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Alzheimer Disease: HELP
Articles by Noel G. Faux
Based on 20 articles published since 2010
(Why 20 articles?)
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Between 2010 and 2020, N. Faux wrote the following 20 articles about Alzheimer Disease.
 
+ Citations + Abstracts
1 Clinical Trial PBT2 rapidly improves cognition in Alzheimer's Disease: additional phase II analyses. 2010

Faux, Noel G / Ritchie, Craig W / Gunn, Adam / Rembach, Alan / Tsatsanis, Andrew / Bedo, Justin / Harrison, John / Lannfelt, Lars / Blennow, Kaj / Zetterberg, Henrik / Ingelsson, Martin / Masters, Colin L / Tanzi, Rudolph E / Cummings, Jeffrey L / Herd, Caroline M / Bush, Ashley I. ·Mental Health Research Institute, The University of Melbourne, Parkville, VIC, Australia. ·J Alzheimers Dis · Pubmed #20164561.

ABSTRACT: PBT2 is a copper/zinc ionophore that rapidly restores cognition in mouse models of Alzheimer's disease (AD). A recent Phase IIa double-blind, randomized, placebo-controlled trial found that the 250 mg dose of PBT2 was well-tolerated, significantly lowered cerebrospinal fluid (CSF) levels of amyloid-beta42, and significantly improved executive function on a Neuro-psychological Test Battery (NTB) within 12 weeks of treatment in patients with AD. In the post-hoc analysis reported here, the cognitive, blood marker, and CSF neurochemistry outcomes from the trial were subjected to further analysis. Ranking the responses to treatment after 12 weeks with placebo, PBT2 50 mg, and PBT2 250 mg revealed that the proportions of patients showing improvement on NTB Composite or Executive Factor z-scores were significantly greater in the PBT2 250 mg group than in the placebo group. Receiver-operator characteristic analyses revealed that the probability of an improver at any level coming from the PBT2 250 mg group was significantly greater, compared to placebo, for Composite z-scores (Area Under the Curve [AUC] =0.76, p=0.0007), Executive Factor z-scores (AUC =0.93, p=1.3 x 10(-9)), and near-significant for the ADAS-cog (AUC =0.72, p=0.056). There were no correlations between changes in CSF amyloid-beta or tau species and cognitive changes. These findings further encourage larger-scale testing of PBT2 for AD.

2 Article Predicting Alzheimer disease from a blood-based biomarker profile: A 54-month follow-up. 2016

Burnham, Samantha C / Rowe, Christopher C / Baker, David / Bush, Ashley I / Doecke, James D / Faux, Noel G / Laws, Simon M / Martins, Ralph N / Maruff, Paul / Macaulay, S Lance / Rainey-Smith, Stephanie / Savage, Greg / Ames, David / Masters, Colin L / Wilson, William / Villemagne, Victor L. ·From eHealth (S.C.B.), CSIRO Health and Biosecurity, Floreat · Department of Nuclear Medicine and Centre for PET (C.C.R.), Austin Health, Heidelberg · Department of Medicine (C.C.R., V.L.V.), Austin Health, University of Melbourne, Heidelberg, Australia · Janssen Research and Development (D.B.), Titusville, NJ · Mental Health Research Institute (A.I.B., N.G.F.), Academic Unit for Psychiatry of Old Age, Department of Psychiatry (D.A.), and The Florey Institute (C.L.M., V.L.V.), University of Melbourne, Parkville · eHealth (J.D.D.), CSIRO Health and Biosecurity, Herston · Centre of Excellence for Alzheimer's Disease Research & Care (S.M.L., R.N.M., S.R.-S.), School of Medical Sciences, Edith Cowan University, Joondalup · School of Biomedical Sciences (S.M.L.), Faculty of Health Sciences, Curtin University, Bentley · Sir James McCusker Alzheimer's Disease Research Unit (Hollywood Private Hospital) (R.N.M., S.R.-S.), Perth · Cogstate (P.M.), Melbourne · CSIRO Food and Nutrition Flagship (S.L.M.), Melbourne · Department of Psychology (G.S.), Macquarie University, Sydney · and eHealth (W.W.), CSIRO Health and Biosecurity, North Ryde, Australia. ·Neurology · Pubmed #27534714.

ABSTRACT: OBJECTIVE: We assessed a blood-based signature, which previously demonstrated high accuracy at stratifying individuals with high or low neocortical β-amyloid burden (NAB), to determine whether it could also identify individuals at risk of progression to Alzheimer disease (AD) within 54 months. METHODS: We generated the blood-based signature for 585 healthy controls (HCs) and 74 participants with mild cognitive impairment (MCI) from the Australian Imaging, Biomarkers and Lifestyle Study who underwent clinical reclassification (blinded to biomarker findings) at 54-month follow-up. The individuals were split into estimated high and low NAB groups based on a cutoff of 1.5 standardized uptake value ratio. We assessed the predictive accuracy of the high and low NAB groupings based on progression to mild cognitive impairment or AD according to clinical reclassification at 54-month follow-up. RESULTS: Twelve percent of HCs with estimated high NAB progressed in comparison to 5% of HCs with estimated low NAB (odds ratio = 2.4). Forty percent of the participants with MCI who had estimated high NAB progressed in comparison to 5% of the participants with MCI who had estimated low NAB (odds ratio = 12.3). These ratios are in line with those reported for Pittsburgh compound B-PET results. Individuals with estimated high NAB had faster rates of memory decline than those with estimated low NAB. CONCLUSION: These findings suggest that a simple blood-based signature not only provides estimates of NAB but also predicts cognitive decline and disease progression, identifying individuals at risk of progressing toward AD at the prodromal and preclinical stages.

3 Article Lead and manganese levels in serum and erythrocytes in Alzheimer's disease and mild cognitive impairment: results from the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing. 2016

Hare, Dominic J / Faux, Noel G / Roberts, Blaine R / Volitakis, Irene / Martins, Ralph N / Bush, Ashley I. ·Elemental Bio-imaging Facility, University of Technology Sydney, Broadway, New South Wales, Australia. dominic.hare@uts.edu.au and The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia. ashley.bush@florey.edu.au. · The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia. ashley.bush@florey.edu.au and IBM Research - Australia, Carlton, Victoria, Australia. · The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia. ashley.bush@florey.edu.au and Cooperative Research Centre for Mental Health, Carlton South, Victoria, Australia. · The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia. ashley.bush@florey.edu.au. · Cooperative Research Centre for Mental Health, Carlton South, Victoria, Australia and The School of Medical Sciences, Edith Cowan University, Joondalup, Western Australia, Australia and The McCusker Alzheimer's Research Foundation, Hollywood Private Hospital, Nedlands, Western Australia, Australia and The Centre of Excellence for Alzheimer's Disease Research and Care, Edith Cowan University, Joondalup, Western Australia, Australia. ·Metallomics · Pubmed #26962965.

ABSTRACT: We examined serum and erythrocyte lead and manganese levels in the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing (AIBL), which contains over 1000 registrants including over 200 cases of Alzheimer's disease (AD) and 100 mildly cognitively impaired (MCI) individuals. After correcting for confounding effects of age, collection site and sex, we found a significant decrease in serum manganese levels in AD subjects compared to healthy controls. Analysis of smaller subset of erythrocytes revealed no difference in either lead or manganese levels in AD. Although lead and manganese have neurotoxic effects and may be involved in AD pathology, our results showed that neither metal in serum nor erythrocytes are suitable biomarkers in our cohort. However, prospective studies might reveal whether the burden of either metal modifies disease outcomes.

4 Article Ferritin levels in the cerebrospinal fluid predict Alzheimer's disease outcomes and are regulated by APOE. 2015

Ayton, Scott / Faux, Noel G / Bush, Ashley I / Anonymous501060. ·Oxidation Biology Unit, The Florey Institute for Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria 3052, Australia. · 1] Bioinformatics Core, The Florey Institute for Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria 3052, Australia [2] Cooperative Research Center for Mental Health, Parkville, Victoria 3052, Australia. · 1] Oxidation Biology Unit, The Florey Institute for Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria 3052, Australia [2] Cooperative Research Center for Mental Health, Parkville, Victoria 3052, Australia. ·Nat Commun · Pubmed #25988319.

ABSTRACT: Brain iron elevation is implicated in Alzheimer's disease (AD) pathogenesis, but the impact of iron on disease outcomes has not been previously explored in a longitudinal study. Ferritin is the major iron storage protein of the body; by using cerebrospinal fluid (CSF) levels of ferritin as an index, we explored whether brain iron status impacts longitudinal outcomes in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. We show that baseline CSF ferritin levels were negatively associated with cognitive performance over 7 years in 91 cognitively normal, 144 mild cognitive impairment (MCI) and 67 AD subjects, and predicted MCI conversion to AD. Ferritin was strongly associated with CSF apolipoprotein E levels and was elevated by the Alzheimer's risk allele, APOE-ɛ4. These findings reveal that elevated brain iron adversely impacts on AD progression, and introduce brain iron elevation as a possible mechanism for APOE-ɛ4 being the major genetic risk factor for AD.

5 Article Decreased plasma iron in Alzheimer's disease is due to transferrin desaturation. 2015

Hare, Dominic J / Doecke, James D / Faux, Noel G / Rembach, Alan / Volitakis, Irene / Fowler, Christopher J / Grimm, Rudolf / Doble, Philip A / Cherny, Robert A / Masters, Colin L / Bush, Ashley I / Roberts, Blaine R. ·†Elemental Bio-imaging Facility, University of Technology Sydney, Broadway, New South Wales 2007, Australia. · ‡The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria 3010, Australia. · §Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States. · ∥The Australian eHealth Research Centre, Herston, Queensland 4006, Australia. · ⊥CSIRO Preventative Health Flagship, Molecular Science and Engineering, Parkville, Victoria 3052, Australia. · #Cooperative Research Centre for Mental Health, Carlton South, Victoria 3053, Australia. · ∇Agilent Technologies, Santa Clara, California 95051, United States. ·ACS Chem Neurosci · Pubmed #25588002.

ABSTRACT: Plasma iron levels are decreased in Alzheimer's disease (AD) and associated with an idiopathic anemia. We examined iron-binding plasma proteins from AD patients and healthy controls from the Australian Imaging, Biomarkers and Lifestyle (AIBL) Flagship Study of Ageing using size exclusion chromatography-inductively coupled plasma-mass spectrometry. Peak area corresponding to transferrin (Tf) saturation was directly compared to routine pathological testing. We found a significant decrease in transferrin-associated iron in AD that was missed by routine pathological tests of transferrin saturation, and that was able to discriminate between AD and controls. The AD cases showed no significant difference in transferrin concentration, only a decrease in total transferrin-bound iron. These findings support that a previously identified decrease in plasma iron levels in AD patients within the AIBL study is attributable to decreased loading of iron into transferrin, and that this subtle but discriminatory change is not observed through routine pathological testing.

6 Article Peripheral α-defensins 1 and 2 are elevated in Alzheimer's disease. 2015

Watt, Andrew D / Perez, Keyla A / Ang, Ching-Seng / O'Donnell, Paul / Rembach, Alan / Pertile, Kelly K / Rumble, Rebecca L / Trounson, Brett O / Fowler, Christopher J / Faux, Noel G / Masters, Colin L / Villemagne, Victor L / Barnham, Kevin J. ·The Florey Institute of Neuroscience and Mental Health, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Melbourne, VIC, Australia The Neuroproteomics Platform, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Melbourne, VIC, Australia. · Mass Spectrometry and Proteomics Facility, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Melbourne, VIC, Australia. · The Florey Institute of Neuroscience and Mental Health, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Melbourne, VIC, Australia. · The Florey Institute of Neuroscience and Mental Health, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Melbourne, VIC, Australia Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, VIC, Australia. · The Florey Institute of Neuroscience and Mental Health, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Melbourne, VIC, Australia Department of Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Melbourne, VIC, Australia The Neuroproteomics Platform, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Melbourne, VIC, Australia. ·J Alzheimers Dis · Pubmed #25408207.

ABSTRACT: Biomarkers enabling the preclinical identification of Alzheimer's disease (AD) remain one of the major unmet challenges in the field. The blood cellular fractions offer a viable alternative to current cerebrospinal fluid and neuroimaging modalities. The current study aimed to replicate our earlier reports of altered binding within the AD-affected blood cellular fraction to copper-loaded immobilized metal affinity capture (IMAC) arrays. IMAC and anti-amyloid-β (Aβ) antibody arrays coupled with mass spectrometry were used to analyze blood samples collected from 218 participants from within the AIBL Study of Aging. Peripheral Aβ was fragile and prone to degradation in the AIBL samples, even when stored at -80°C. IMAC analysis of the AIBL samples lead to the isolation and identification of alpha-defensins 1 and 2 at elevated levels in the AD periphery, validating earlier findings. Alpha-defensins 1 and 2 were elevated in AD patients indicating that an inflammatory phenotype is present in the AD periphery; however, peripheral Aβ levels are required to supplement their prognostic power.

7 Article An anemia of Alzheimer's disease. 2014

Faux, N G / Rembach, A / Wiley, J / Ellis, K A / Ames, D / Fowler, C J / Martins, R N / Pertile, K K / Rumble, R L / Trounson, B / Masters, C L / Anonymous3270781 / Bush, A I. ·1] The Florey Institute for Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia [2] Cooperative Research Center for Mental Health, Carlton South, Victoria, Australia. · The Florey Institute for Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia. · Department of Psychiatry, The University of Melbourne, Parkville, Victoria, Australia. · National Ageing Research Institute, Royal Melbourne Hospital, Parkville, Victoria, Australia. · 1] Centre of Excellence for Alzheimer's Disease Research & Care, School of Exercise Biomedical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia [2] Sir James McCusker Alzheimer's Disease Research Unit, Hollywood Private Hospital, Perth, Western Australia, Australia. ·Mol Psychiatry · Pubmed #24419041.

ABSTRACT: Lower hemoglobin is associated with cognitive impairment and Alzheimer's disease (AD). Since brain iron homeostasis is perturbed in AD, we investigated whether this is peripherally reflected in the hematological and related blood chemistry values from the Australian Imaging Biomarker and Lifestyle (AIBL) study (a community-based, cross-sectional cohort comprising 768 healthy controls (HC), 133 participants with mild cognitive impairment (MCI) and 211 participants with AD). We found that individuals with AD had significantly lower hemoglobin, mean cell hemoglobin concentrations, packed cell volume and higher erythrocyte sedimentation rates (adjusted for age, gender, APOE-ɛ4 and site). In AD, plasma iron, transferrin, transferrin saturation and red cell folate levels exhibited a significant distortion of their customary relationship to hemoglobin levels. There was a strong association between anemia and AD (adjusted odds ratio (OR)=2.43, confidence interval (CI) (1.31, 4.54)). Moreover, AD emerged as a strong risk factor for anemia on step-down regression, even when controlling for all other available explanations for anemia (adjusted OR=3.41, 95% CI (1.68, 6.92)). These data indicated that AD is complicated by anemia, which may itself contribute to cognitive decline.

8 Article Among vitamin B12 deficient older people, high folate levels are associated with worse cognitive function: combined data from three cohorts. 2014

Moore, Eileen M / Ames, David / Mander, Alastair G / Carne, Ross P / Brodaty, Henry / Woodward, Michael C / Boundy, Karyn / Ellis, Kathryn A / Bush, Ashley I / Faux, Noel G / Martins, Ralph N / Masters, Colin L / Rowe, Christopher C / Szoeke, Cassandra / Watters, David A. ·Department of Psychiatry, The University of Melbourne, Parkville, VIC, Australia Barwon Health, Geelong, VIC, Australia. · Department of Psychiatry, The University of Melbourne, Parkville, VIC, Australia National Ageing Research Institute, Parkville, VIC, Australia. · Barwon Health, Geelong, VIC, Australia. · Barwon Health, Geelong, VIC, Australia Deakin University, School of Medicine, Waurn Ponds, VIC, Australia. · The University of New South Wales, Centre for Healthy Brain Ageing and Dementia Collaborative Research Centre, Sydney, NSW, Australia Aged Care Psychiatry, Prince of Wales Hospital, Randwick, NSW, Australia. · Austin Health, Heidelberg Repatriation Hospital, Heidelberg, VIC, Australia. · The Queen Elizabeth Hospital, Woodville South, SA, Australia. · Department of Psychiatry, The University of Melbourne, Parkville, VIC, Australia National Ageing Research Institute, Parkville, VIC, Australia The University of Melbourne, Florey Institute of Neuroscience & Mental Health, Parkville, VIC, Australia. · The University of Melbourne, Florey Institute of Neuroscience & Mental Health, Parkville, VIC, Australia Department of Pathology, The University of Melbourne, Parkville, VIC, Australia. · The University of Melbourne, Florey Institute of Neuroscience & Mental Health, Parkville, VIC, Australia. · Edith Cowan University, Centre of Excellence for Alzheimer's Disease Research & Care, School of Exercise, Biomedical and Health Sciences, Joondalup, WA, Australia Sir James McCusker Alzheimer's Disease Research Unit (Hollywood Private Hospital), Neurosciences Unit, Health Department of Western Australia, Perth, WA, Australia. · The University of Melbourne, Florey Institute of Neuroscience & Mental Health, Parkville, VIC, Australia The University of Melbourne, Centre for Neuroscience, Parkville, VIC, Australia. · Austin PET centre, Austin Hospital, Heidelberg, VIC, Australia. · National Ageing Research Institute, Parkville, VIC, Australia Preventative Health Flagship, Commonwealth Science Industry Research Organization, Parkville, VIC, Australia. ·J Alzheimers Dis · Pubmed #24246419.

ABSTRACT: BACKGROUND: Folate fortification of food aims to reduce the number of babies born with neural tube defects, but has been associated with cognitive impairment when vitamin B12 levels are deficient. Given the prevalence of low vitamin B12 levels among the elderly, and the global deployment of food fortification programs, investigation of the associations between cognitive impairment, vitamin B12, and folate are needed. OBJECTIVE: To investigate the associations of serum vitamin B12, red cell folate, and cognitive impairment. METHODS: Data were collected on 1,354 subjects in two studies investigating cognitive impairment, and from patients attending for assessment or management of memory problems in the Barwon region of south eastern Australia between 2001 and 2011. Eligible subjects who had blood measurements of vitamin B12 and red cell folate taken within six months of cognitive testing were included. Subjects with stroke or neurodegenerative diseases other than Alzheimer's disease were excluded. A Mini-Mental State Examination score of <24 was used to define impaired cognitive function. RESULTS: Participants with low serum vitamin B12 (<250 pmol/L) and high red cell folate (>1,594 nmol/L) levels were more likely to have impaired cognitive performance (adjusted odds ratio (AOR) 3.45, 95% confidence interval (CI): 1.60-7.43, p = 0.002) when compared to participants with biochemical measurements that were within the normal ranges. Participants with high folate levels, but normal serum vitamin B12, were also more likely to have impaired cognitive performance (AOR 1.74, 95% CI: 1.03-2.95, p = 0.04). CONCLUSIONS: High folate or folic acid supplements may be detrimental to cognition in older people with low vitamin B12 levels. This topic is of global significance due to the wide distribution of food fortification programs, so prospective studies should be a high priority.

9 Article A blood-based predictor for neocortical Aβ burden in Alzheimer's disease: results from the AIBL study. 2014

Burnham, S C / Faux, N G / Wilson, W / Laws, S M / Ames, D / Bedo, J / Bush, A I / Doecke, J D / Ellis, K A / Head, R / Jones, G / Kiiveri, H / Martins, R N / Rembach, A / Rowe, C C / Salvado, O / Macaulay, S L / Masters, C L / Villemagne, V L / Anonymous620757 / Anonymous630757. ·CSIRO Preventative Health Flagship: Mathematics, Informatics and Statistics, Perth, WA, Australia. · Mental Health Research Institute (MHRI), The University of Melbourne, Parkville, VIC, Australia. · CSIRO Preventative Health Flagship: Mathematics, Informatics and Statistics, North Ryde, NSW, Australia. · 1] Centre of Excellence for Alzheimer's Disease Research & Care, School of Medical Sciences, Edith Cowan University, Joondalup, WA, Australia [2] Sir James McCusker Alzheimer's Disease Research Unit, Hollywood Private Hospital, Perth, WA, Australia. · 1] Academic Unit for Psychiatry of Old Age, Department of Psychiatry, The University of Melbourne, Parkville, VIC, Australia [2] National Ageing Research Institute, Parkville, VIC, Australia. · Victorian Research Laboratory, National ICT of Australia (NICTA), Melbourne, VIC, Australia. · CSIRO Preventative Health Flagship: Mathematics, Informatics and Statistics, Herston, QLD, Australia. · Academic Unit for Psychiatry of Old Age, Department of Psychiatry, The University of Melbourne, Parkville, VIC, Australia. · CSIRO Preventative Health Flagship: Health and Life Sciences, Urrbrae, SA, Australia. · 1] Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, VIC, Australia [2] Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, VIC, Australia. · CSIRO Preventative Health Flagship: Information and Communication Technology, Herston, QLD, Australia. · CSIRO Preventative Health Flagship: Materials Science and Engineering, Parkville, VIC, Australia. · Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, VIC, Australia. ·Mol Psychiatry · Pubmed #23628985.

ABSTRACT: Dementia is a global epidemic with Alzheimer's disease (AD) being the leading cause. Early identification of patients at risk of developing AD is now becoming an international priority. Neocortical Aβ (extracellular β-amyloid) burden (NAB), as assessed by positron emission tomography (PET), represents one such marker for early identification. These scans are expensive and are not widely available, thus, there is a need for cheaper and more widely accessible alternatives. Addressing this need, a blood biomarker-based signature having efficacy for the prediction of NAB and which can be easily adapted for population screening is described. Blood data (176 analytes measured in plasma) and Pittsburgh Compound B (PiB)-PET measurements from 273 participants from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study were utilised. Univariate analysis was conducted to assess the difference of plasma measures between high and low NAB groups, and cross-validated machine-learning models were generated for predicting NAB. These models were applied to 817 non-imaged AIBL subjects and 82 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) for validation. Five analytes showed significant difference between subjects with high compared to low NAB. A machine-learning model (based on nine markers) achieved sensitivity and specificity of 80 and 82%, respectively, for predicting NAB. Validation using the ADNI cohort yielded similar results (sensitivity 79% and specificity 76%). These results show that a panel of blood-based biomarkers is able to accurately predict NAB, supporting the hypothesis for a relationship between a blood-based signature and Aβ accumulation, therefore, providing a platform for developing a population-based screen.

10 Article Changes in plasma amyloid beta in a longitudinal study of aging and Alzheimer's disease. 2014

Rembach, Alan / Faux, Noel G / Watt, Andrew D / Pertile, Kelly K / Rumble, Rebecca L / Trounson, Brett O / Fowler, Christopher J / Roberts, Blaine R / Perez, Keyla A / Li, Qiao-Xin / Laws, Simon M / Taddei, Kevin / Rainey-Smith, Stephanie / Robertson, Joanne S / Vandijck, Manu / Vanderstichele, Hugo / Barnham, Kevin J / Ellis, Kathryn A / Szoeke, Cassandra / Macaulay, Lance / Rowe, Christopher C / Villemagne, Victor L / Ames, David / Martins, Ralph N / Bush, Ashley I / Masters, Colin L / Anonymous5630752. ·The Mental Health Research Institute, The University of Melbourne, Victoria, Australia. Electronic address: a.rembach@unimelb.edu.au. · The Mental Health Research Institute, The University of Melbourne, Victoria, Australia. · Sir James McCusker Alzheimer's Disease Research Unit (Hollywood Private Hospital), Perth, Western Australia, Australia; Centre of Excellence for Alzheimer's Disease Research & Care, School of Medical Sciences, Edith Cowan University, Joondalup. Western Australia, Australia. · Department of Diagnostic Development, Innogenetics NV, Ghent, Belgium. · Department of Diagnostic Development, Innogenetics NV, Ghent, Belgium; Biomarkable, Gent, Belgium. · The Mental Health Research Institute, The University of Melbourne, Victoria, Australia; Department of Psychiatry, St George's Hospital, University of Melbourne, Victoria, Australia; National Ageing Research Institute, Parkville, Victoria, Australia. · Department of Psychiatry, St George's Hospital, University of Melbourne, Victoria, Australia; National Ageing Research Institute, Parkville, Victoria, Australia. · CSIRO Molecular and Health Technologies, Parkville, Victoria, Australia. · Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, Victoria, Australia. · The Mental Health Research Institute, The University of Melbourne, Victoria, Australia; Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, Victoria, Australia. · National Ageing Research Institute, Parkville, Victoria, Australia. ·Alzheimers Dement · Pubmed #23491263.

ABSTRACT: BACKGROUND: A practical biomarker is required to facilitate the preclinical diagnosis of Alzheimer's disease (AD). METHODS: Plasma amyloid beta (Aβ)1-40, Aβ1-42, Aβn-40, and Aβn-42 peptides were measured at baseline and after 18 months in 771 participants from the Australian Imaging Biomarkers and Lifestyle (AIBL) study of aging. Aβ peptide levels were compared with clinical pathology, neuroimaging and neuropsychological measurements. RESULTS: Although inflammatory and renal function covariates influenced plasma Aβ levels significantly, a decrease in Aβ1-42/Aβ1-40 was observed in patients with AD, and was also inversely correlated with neocortical amyloid burden. During the 18 months, plasma Aβ1-42 decreased in subjects with mild cognitive impairment (MCI) and in those transitioning from healthy to MCI. CONCLUSION: Our findings are consistent with a number of published plasma Aβ studies and, although the prognostic value of individual measures in any given subject is limited, the diagnostic contribution of plasma Aβ may demonstrate utility when combined with a panel of peripheral biomarkers.

11 Article Associations between gonadotropins, testosterone and β amyloid in men at risk of Alzheimer's disease. 2014

Verdile, G / Laws, S M / Henley, D / Ames, D / Bush, A I / Ellis, K A / Faux, N G / Gupta, V B / Li, Q-X / Masters, C L / Pike, K E / Rowe, C C / Szoeke, C / Taddei, K / Villemagne, V L / Martins, R N / Anonymous2020740. ·1] Centre of Excellence for Alzheimer's Disease Research & Care, School of Medical Sciences, Edith Cowan University, Joondalup, Western Australia, Australia [2] Sir James McCusker Alzheimer's Disease Research Unit (Hollywood Private Hospital), Perth, Western Australia, Australia. · 1] Centre of Excellence for Alzheimer's Disease Research & Care, School of Medical Sciences, Edith Cowan University, Joondalup, Western Australia, Australia [2] Sir James McCusker Alzheimer's Disease Research Unit (Hollywood Private Hospital), Perth, Western Australia, Australia [3] Co-operative Research Centre for Mental Health, http://www.mentalhealthcrc.com. · 1] Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia [2] School of Medicine and Pharmacology, University of Western Australia, Crawley, Western Australia, Australia. · 1] Academic Unit for Psychiatry of Old Age, Department of Psychiatry, The University of Melbourne, St Vincent's Aged Psychiatry Service, St George's Hospital, Melbourne, Victoria, Australia [2] National Ageing Research Institute, Parkville, Victoria, Australia. · 1] Co-operative Research Centre for Mental Health, http://www.mentalhealthcrc.com [2] Mental Health Research Institute, The University of Melbourne, Parkville, Victoria, Australia [3] Centre for Neuroscience, The University of Melbourne, Parkville, Victoria, Australia. · 1] Academic Unit for Psychiatry of Old Age, Department of Psychiatry, The University of Melbourne, St Vincent's Aged Psychiatry Service, St George's Hospital, Melbourne, Victoria, Australia [2] National Ageing Research Institute, Parkville, Victoria, Australia [3] Mental Health Research Institute, The University of Melbourne, Parkville, Victoria, Australia. · 1] Mental Health Research Institute, The University of Melbourne, Parkville, Victoria, Australia [2] Centre for Neuroscience, The University of Melbourne, Parkville, Victoria, Australia. · 1] Mental Health Research Institute, The University of Melbourne, Parkville, Victoria, Australia [2] Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia. · 1] Mental Health Research Institute, The University of Melbourne, Parkville, Victoria, Australia [2] Centre for Neuroscience, The University of Melbourne, Parkville, Victoria, Australia [3] Department of Nuclear Medicine & Centre for PET, Austin Health, Heidelberg, Victoria, Australia [4] School of Psychological Science, La Trobe University, Bundoora, Victoria Australia. · Department of Nuclear Medicine & Centre for PET, Austin Health, Heidelberg, Victoria, Australia. · 1] National Ageing Research Institute, Parkville, Victoria, Australia [2] CSIRO, Parkville, Victoria, Australia. · 1] Mental Health Research Institute, The University of Melbourne, Parkville, Victoria, Australia [2] Department of Nuclear Medicine & Centre for PET, Austin Health, Heidelberg, Victoria, Australia. ·Mol Psychiatry · Pubmed #23089633.

ABSTRACT: Testosterone and gonadotropins have been associated with cognitive decline in men and the modulation of β amyloid (Aβ) metabolism. The relatively few studies that have investigated whether changes in one or a combination of these hormones influence Aβ levels have focused primarily on plasma Aβ(1-40) and not on the more pathogenic Aβ(1-42). Currently, no study has investigated whether these hormones are associated with an increase in brain amyloid deposition, ante mortem. Through the highly characterised Australian imaging, biomarkers and lifestyle study, we have determined the impact of these hormones on plasma Aβ levels and brain amyloid burden (Pittsburgh compound B (PiB) retention). Spearman's rank correlation and linear regression analysis was carried out across the cohort and within subclassifications. Luteinizing hormone (LH) was the only variable shown, in the total cohort, to have a significant impact on plasma Aβ(1-40) and Aβ(1-42) levels (beta=0.163, P<0.001; beta=0.446, P<0.001). This held in subjective memory complainers (SMC) (Aβ(1-40); beta=0.208, P=0.017; Aβ(1-42); beta=0.215, P=0.017) but was absent in mild cognitive impairment (MCI) and Alzheimer's disease (AD) groups. In SMC, increased frequency of the APOE-ɛ4 allele (beta=0.536, P<0.001) and increasing serum LH levels (beta=0.421, P=0.004) had a significant impact on PiB retention. Whereas in MCI, PiB retention was associated with increased APOE-ɛ4 allele copy number (beta=0.674, P<0.001) and decreasing calculated free testosterone (beta=-0.303, P=0.043). These findings suggest a potential progressive involvement of LH and testosterone in the early preclinical stages of AD. Furthermore, these hormones should be considered while attempting to predict AD at these earliest stages of the disease.

12 Article Longitudinal analysis of serum copper and ceruloplasmin in Alzheimer's disease. 2013

Rembach, Alan / Doecke, James D / Roberts, Blaine R / Watt, Andrew D / Faux, Noel G / Volitakis, Irene / Pertile, Kelly K / Rumble, Rebecca L / Trounson, Brett O / Fowler, Christopher J / Wilson, William / Ellis, Kathryn A / Martins, Ralph N / Rowe, Christopher C / Villemagne, Victor L / Ames, David / Masters, Colin L / AIBL research group, ? / Bush, Ashley I. ·The Mental Health Research Institute, The University of Melbourne, VIC, Australia. ·J Alzheimers Dis · Pubmed #23168449.

ABSTRACT: BACKGROUND: Several studies have reported that peripheral levels of copper and ceruloplasmin (CP) can differentiate patients with Alzheimer's disease (AD) from non-AD cases. The aim of this study was to determine the diagnostic value of serum copper, CP, and non-CP copper levels in a large cohort of AD subjects. METHODS: Serum copper and CP concentrations were measured at baseline and at 18-months in participants from the Australian Imaging Biomarkers and Lifestyle Study of Ageing. Cross-sectional and longitudinal analyses were conducted using both univariate and multivariate testing adjusting for age, gender, total protein, and ApoE ε4 genotype status. RESULTS: There was no significant difference in levels of serum copper or CP between the AD and healthy control groups, however, we identified a near-significant decrease in non-CP copper in the mild cognitive impairment and AD groups at baseline (p = 0.02) that was significant at 18-months (p = 0.003). CONCLUSION: Our results suggest that there may be decreased non-CP copper levels in mild cognitive impairment and AD, which is consistent with diminished copper-dependent biochemical activities described in AD.

13 Article Blood-based protein biomarkers for diagnosis of Alzheimer disease. 2012

Doecke, James D / Laws, Simon M / Faux, Noel G / Wilson, William / Burnham, Samantha C / Lam, Chiou-Peng / Mondal, Alinda / Bedo, Justin / Bush, Ashley I / Brown, Belinda / De Ruyck, Karl / Ellis, Kathryn A / Fowler, Christopher / Gupta, Veer B / Head, Richard / Macaulay, S Lance / Pertile, Kelly / Rowe, Christopher C / Rembach, Alan / Rodrigues, Mark / Rumble, Rebecca / Szoeke, Cassandra / Taddei, Kevin / Taddei, Tania / Trounson, Brett / Ames, David / Masters, Colin L / Martins, Ralph N / Anonymous4610731 / Anonymous4620731. ·The Australian E-Health Research Centre, Royal Brisbane and Women's Hospital, Herston, Queensland, Australia. ·Arch Neurol · Pubmed #22801742.

ABSTRACT: OBJECTIVE: To identify plasma biomarkers for the diagnosis of Alzheimer disease (AD). DESIGN: Baseline plasma screening of 151 multiplexed analytes combined with targeted biomarker and clinical pathology data. SETTING: General community-based, prospective, longitudinal study of aging. PARTICIPANTS: A total of 754 healthy individuals serving as controls and 207 participants with AD from the Australian Imaging Biomarker and Lifestyle study (AIBL) cohort with identified biomarkers that were validated in 58 healthy controls and 112 individuals with AD from the Alzheimer Disease Neuroimaging Initiative (ADNI) cohort. RESULTS: A biomarker panel was identified that included markers significantly increased (cortisol, pancreatic polypeptide, insulinlike growth factor binding protein 2, β(2) microglobulin, vascular cell adhesion molecule 1, carcinoembryonic antigen, matrix metalloprotein 2, CD40, macrophage inflammatory protein 1α, superoxide dismutase, and homocysteine) and decreased (apolipoprotein E, epidermal growth factor receptor, hemoglobin, calcium, zinc, interleukin 17, and albumin) in AD. Cross-validated accuracy measures from the AIBL cohort reached a mean (SD) of 85% (3.0%) for sensitivity and specificity and 93% (3.0) for the area under the receiver operating characteristic curve. A second validation using the ADNI cohort attained accuracy measures of 80% (3.0%) for sensitivity and specificity and 85% (3.0) for area under the receiver operating characteristic curve. CONCLUSIONS: This study identified a panel of plasma biomarkers that distinguish individuals with AD from cognitively healthy control subjects with high sensitivity and specificity. Cross-validation within the AIBL cohort and further validation within the ADNI cohort provides strong evidence that the identified biomarkers are important for AD diagnosis.

14 Article Homocysteine, vitamin B12, and folic acid levels in Alzheimer's disease, mild cognitive impairment, and healthy elderly: baseline characteristics in subjects of the Australian Imaging Biomarker Lifestyle study. 2011

Faux, Noel G / Ellis, Kathryn A / Porter, Lorine / Fowler, Chris J / Laws, Simon M / Martins, Ralph N / Pertile, Kelly K / Rembach, Alan / Rowe, Chris C / Rumble, Rebecca L / Szoeke, Cassandra / Taddei, Kevin / Taddei, Tania / Trounson, Brett O / Villemagne, Victor L / Ward, Vanessa / Ames, David / Masters, Colin L / Bush, Ashley I. ·The Mental Health Research Institute, The University of Melbourne, Parkville, VIC, Australia. ·J Alzheimers Dis · Pubmed #21891867.

ABSTRACT: There is some debate regarding the differing levels of plasma homocysteine, vitamin B12 and serum folate between healthy controls (HC), mild cognitive impairment (MCI), and Alzheimer's disease (AD). As part of the Australian Imaging Biomarker Lifestyle (AIBL) study of aging cohort, consisting of 1,112 participants (768 HC, 133 MCI patients, and 211 AD patients), plasma homocysteine, vitamin B12, and serum and red cell folate were measured at baseline to investigate their levels, their inter-associations, and their relationships with cognition. The results of this cross-sectional study showed that homocysteine levels were increased in female AD patients compared to female HC subjects (+16%, p-value < 0.001), but not in males. Red cell folate, but not serum folate, was decreased in AD patients compared to HC (-10%, p-value = 0.004). Composite z-scores of short- and long-term episodic memory, total episodic memory, and global cognition all showed significant negative correlations with homocysteine, in all clinical categories. Increasing red cell folate had a U-shaped association with homocysteine, so that high red cell folate levels were associated with worse long-term episodic memory, total episodic memory, and global cognition. These findings underscore the association of plasma homocysteine with cognitive deterioration, although not unique to AD, and identified an unexpected abnormality of red cell folate.

15 Article Effects of anticholinergic drugs on cognitive function in older Australians: results from the AIBL study. 2011

Sittironnarit, Gobhathai / Ames, David / Bush, Ashley I / Faux, Noel / Flicker, Leon / Foster, Jonathan / Hilmer, Sarah / Lautenschlager, Nicola T / Maruff, Paul / Masters, Colin L / Martins, Ralph N / Rowe, Christopher / Szoeke, Cassandra / Ellis, Kathryn A / Anonymous12770688. ·Department of Psychiatry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. ·Dement Geriatr Cogn Disord · Pubmed #21389718.

ABSTRACT: BACKGROUND/AIMS: The nature and extent of adverse cognitive effects due to the prescription of anticholinergic drugs in older people with and without dementia is unclear. METHODS: We calculated the anticholinergic load (ACL) of medications taken by participants of the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of ageing, a cohort of 211 Alzheimer's disease (AD) patients, 133 mild cognitive impairment (MCI) patients and 768 healthy controls (HC) all aged over 60 years. The association between ACL and cognitive function was examined for each diagnostic group (HC, MCI, AD). RESULTS: A high ACL within the HC group was associated with significantly slower response speeds for the Stroop color and incongruent trials. No other significant relationships between ACL and cognition were noted. CONCLUSION: In this large cohort, prescribed anticholinergic drugs appeared to have modest effects upon psychomotor speed and executive function, but not on other areas of cognition in healthy older adults.

16 Article Increasing the predictive accuracy of amyloid-β blood-borne biomarkers in Alzheimer's disease. 2011

Watt, Andrew D / Perez, Keyla A / Faux, Noel G / Pike, Kerryn E / Rowe, Christopher C / Bourgeat, Pierrick / Salvado, Olivier / Masters, Colin L / Villemagne, Victor L / Barnham, Kevin J. ·Department of Pathology, The University of Melbourne, Parkville, Melbourne, Victoria, Australia. ·J Alzheimers Dis · Pubmed #21157020.

ABSTRACT: Diagnostic measures for Alzheimer's disease (AD) commonly rely on evaluating the levels of amyloid-β (Aβ) peptides within the cerebrospinal fluid (CSF) of affected individuals. These levels are often combined with levels of an additional non-Aβ marker to increase predictive accuracy. Recent efforts to overcome the invasive nature of CSF collection led to the observation of Aβ species within the blood cellular fraction, however, little is known of what additional biomarkers may be found in this membranous fraction. The current study aimed to undertake a discovery-based proteomic investigation of the blood cellular fraction from AD patients (n = 18) and healthy controls (HC; n = 15) using copper immobilized metal affinity capture and Surface Enhanced Laser Desorption/Ionisation Time-Of-Flight Mass Spectrometry. Three candidate biomarkers were observed which could differentiate AD patients from HC (ROC AUC > 0.8). Bivariate pairwise comparisons revealed significant correlations between these markers and measures of AD severity including; MMSE, composite memory, brain amyloid burden, and hippocampal volume. A partial least squares regression model was generated using the three candidate markers along with blood levels of Aβ. This model was able to distinguish AD from HC with high specificity (90%) and sensitivity (77%) and was able to separate individuals with mild cognitive impairment (MCI) who converted to AD from MCI non-converters. While requiring further characterization, these candidate biomarkers reaffirm the potential efficacy of blood-based investigations into neurodegenerative conditions. Furthermore, the findings indicate that the incorporation of non-amyloid markers into predictive models, function to increase the accuracy of the diagnostic potential of Aβ.

17 Article Larger temporal volume in elderly with high versus low beta-amyloid deposition. 2010

Chételat, Gaël / Villemagne, Victor L / Pike, Kerryn E / Baron, Jean-Claude / Bourgeat, Pierrick / Jones, Gareth / Faux, Noel G / Ellis, Kathryn A / Salvado, Olivier / Szoeke, Cassandra / Martins, Ralph N / Ames, David / Masters, Colin L / Rowe, Christopher C / Anonymous1150669. ·Department of Nuclear Medicine and Centre for PET, Austin Health, 145 Studley Road, Heidelberg, VIC 3084, Australia. chetelat@cyceron.fr ·Brain · Pubmed #20739349.

ABSTRACT: β-Amyloid deposition is one of the main hallmarks of Alzheimer's disease thought to eventually cause neuronal death. Post-mortem and neuroimaging studies have consistently reported cases with documented normal cognition despite high β-amyloid burden. It is of great interest to understand what differentiates these particular subjects from those without β-amyloid deposition or with both β-amyloid deposition and cognitive deficits, i.e. what allows these subjects to resist the damage of the pathological lesions. [¹¹C]Pittsburgh compound B positron emission tomography and magnetic resonance brain scans were obtained in 149 participants including healthy controls and patients with subjective cognitive impairment, mild cognitive impairment and Alzheimer's disease. Magnetic resonance data were compared between high versus low-[11C]Pittsburgh compound B cases, and between high-[¹¹C]Pittsburgh compound B cases with versus those without cognitive deficits. Larger temporal (including hippocampal) grey matter volume, associated with better episodic memory performance, was found in high- versus low-[¹¹C]Pittsburgh compound B healthy controls. The same finding was obtained using different [¹¹C]Pittsburgh compound B thresholds, correcting [¹¹C]Pittsburgh compound B data for partial averaging, using age, education, Mini-Mental State Examination, apolipoprotein E4 and sex-matched subsamples, and using manual hippocampal delineation instead of voxel-based analysis. By contrast, in participants with subjective cognitive impairment, significant grey matter atrophy was found in high-[¹¹C]Pittsburgh compound B cases compared to low-[¹¹C]Pittsburgh compound B cases, as well as in high-[¹¹C]Pittsburgh compound B cases with subjective cognitive impairment, mild cognitive impairment and Alzheimer's disease compared to high-[¹¹C]Pittsburgh compound B healthy controls. Larger grey matter volume in high-[¹¹C]Pittsburgh compound B healthy controls may reflect either a tissue reactive response to β-amyloid or a combination of higher 'brain reserve' and under-representation of subjects with standard/low temporal volume in the high-[¹¹C]Pittsburgh compound B healthy controls. Our complementary analyses tend to support the latter hypotheses. Overall, our findings suggest that the deleterious effects of β-amyloid on cognition may be delayed in those subjects with larger brain (temporal) volume.

18 Article Blood-borne amyloid-beta dimer correlates with clinical markers of Alzheimer's disease. 2010

Villemagne, Victor L / Perez, Keyla A / Pike, Kerryn E / Kok, W Mei / Rowe, Christopher C / White, Anthony R / Bourgeat, Pierrick / Salvado, Olivier / Bedo, Justin / Hutton, Craig A / Faux, Noel G / Masters, Colin L / Barnham, Kevin J. ·Mental Health Research Institute, The University of Melbourne, Parkville, Melbourne, Victoria 3052, Australia. ·J Neurosci · Pubmed #20445057.

ABSTRACT: Alzheimer's disease (AD) is the most common age-related dementia. Unfortunately due to a lack of validated biomarkers definitive diagnosis relies on the histological demonstration of amyloid-beta (Abeta) plaques and tau neurofibrillary tangles. Abeta processing is implicated in AD progression and many therapeutic strategies target various aspects of this biology. While Abeta deposition is the most prominent feature of AD, oligomeric forms of Abeta have been implicated as the toxic species inducing the neuronal dysfunction. Currently there are no methods allowing routine monitoring of levels of such species in living populations. We have used surface enhanced laser desorption ionization time of flight (SELDI-TOF) mass spectrometry incorporating antibody capture to investigate whether the cellular membrane-containing fraction of blood provides a new source of biomarkers. There are significant differences in the mass spectra profiles of AD compared with HC subjects, with significantly higher levels of Abeta monomer and dimer in the blood of AD subjects. Furthermore, levels of these species correlated with clinical markers of AD including brain Abeta burden, cognitive impairment and brain atrophy. These results indicate that fundamental biochemical events relevant to AD can be monitored in blood, and that the species detected may be useful clinical biomarkers for AD.

19 Article Plasma amyloid-beta as a biomarker in Alzheimer's disease: the AIBL study of aging. 2010

Lui, James K / Laws, Simon M / Li, Qiao-Xin / Villemagne, Victor L / Ames, David / Brown, Belinda / Bush, Ashley I / De Ruyck, Karl / Dromey, Jasmin / Ellis, Kathryn A / Faux, Noel G / Foster, Jonathan / Fowler, Christopher / Gupta, Veer / Hudson, Peter / Laughton, Katrina / Masters, Colin L / Pertile, Kelly / Rembach, Alan / Rimajova, Mira / Rodrigues, Mark / Rowe, Christopher C / Rumble, Rebecca / Szoeke, Cassandra / Taddei, Kevin / Taddei, Tania / Trounson, Brett / Ward, Vanessa / Martins, Ralph N / AIBL Research Group, ?. ·Centre of Excellence for Alzheimer's Disease Research & Care, School of Exercise Biomedical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia. ·J Alzheimers Dis · Pubmed #20413897.

ABSTRACT: Amyloid-beta (Abeta) plays a central role in the pathogenesis of Alzheimer's disease (AD) and has been postulated as a potential biomarker for AD. However, there is a lack of consensus as to its suitability as an AD biomarker. The objective of this study was to determine the significance of plasma Abeta as an AD biomarker and its relationship with Abeta load and to determine the effect of different assay methods on the interpretation of Abeta levels. Plasma Abeta1-40, Abeta1-42, and N-terminal cleaved fragments were measured using both a commercial multiplex assay and a well-documented ELISA in 1032 individuals drawn from the well-characterized Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging. Further, Abeta levels were compared to Abeta load derived from positron-emission tomography (PET) with the Pittsburgh compound B (PiB). Lower Abeta1-42 and Abeta1-42/1-40 ratio were observed in patients with AD and inversely correlated with PiB-PET derived Abeta load. However, assay methodology significantly impacted the interpretation of data. The cross-sectional analysis of plasma Abeta isoforms suggests that they may not be sufficient per se to diagnose AD. The value of their measurement in prognosis and monitoring of AD interventions needs further study, in addition to future longitudinal comparisons together with other predictors, which will determine whether plasma Abeta has diagnostic value in a panel of biomarkers.

20 Article A domain level interaction network of amyloid precursor protein and Abeta of Alzheimer's disease. 2010

Perreau, Victoria M / Orchard, Sandra / Adlard, Paul A / Bellingham, Shayne A / Cappai, Roberto / Ciccotosto, Giuseppe D / Cowie, Tiffany F / Crouch, Peter J / Duce, James A / Evin, Genevieve / Faux, Noel G / Hill, Andrew F / Hung, Ya Hui / James, Simon A / Li, Qiao-Xin / Mok, Su San / Tew, Deborah J / White, Anthony R / Bush, Ashley I / Hermjakob, Henning / Masters, Colin L. ·Neuroproteomics and Neurogenomics Platform, National Neurosciences Facility, The University of Melbourne, Parkville, VIC, Australia. vperreau@unimelb.edu.au ·Proteomics · Pubmed #20391539.

ABSTRACT: The primary constituent of the amyloid plaque, beta-amyloid (Abeta), is thought to be the causal "toxic moiety" of Alzheimer's disease. However, despite much work focused on both Abeta and its parent protein, amyloid precursor protein (APP), the functional roles of APP and its cleavage products remain to be fully elucidated. Protein-protein interaction networks can provide insight into protein function, however, high-throughput data often report false positives and are in frequent disagreement with low-throughput experiments. Moreover, the complexity of the CNS is likely to be under represented in such databases. Therefore, we curated the published work characterizing both APP and Abeta to create a protein interaction network of APP and its proteolytic cleavage products, with annotation, where possible, to the level of APP binding domain and isoform. This is the first time that an interactome has been refined to domain level, essential for the interpretation of APP due to the presence of multiple isoforms and processed fragments. Gene ontology and network analysis were used to identify potentially novel functional relationships among interacting proteins.