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Alzheimer Disease: HELP
Articles by Sulantha Mathotaarachchi
Based on 19 articles published since 2010
(Why 19 articles?)
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Between 2010 and 2020, S. Mathotaarachchi wrote the following 19 articles about Alzheimer Disease.
 
+ Citations + Abstracts
1 Article Mild behavioral impairment is associated with β-amyloid but not tau or neurodegeneration in cognitively intact elderly individuals. 2020

Lussier, Firoza Z / Pascoal, Tharick A / Chamoun, Mira / Therriault, Joseph / Tissot, Cécile / Savard, Mélissa / Kang, Min Su / Mathotaarachchi, Sulantha / Benedet, Andrea L / Parsons, Marlee / Qureshi, Muhammad Naveed Iqbal / Thomas, Émilie M / Shin, Monica / Dion, Laurie-Anne / Massarweh, Gassan / Soucy, Jean-Paul / Tsai, I-Huang / Vitali, Paolo / Ismail, Zahinoor / Rosa-Neto, Pedro / Gauthier, Serge. ·Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, Douglas Hospital, McGill University, Montreal, Quebec, Canada. · Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada. · Montreal Neurological Institute, Montreal, Quebec, Canada. · Department of Radiochemistry, McGill University, Montreal, Quebec, Canada. · Alzheimer's Disease Research Unit, The McGill University Research Centre for Studies in Aging, Verdun, Quebec, Canada. · Departments of Psychiatry, Clinical Neurosciences, and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada. · Hotchkiss Brain Institute and O'Brien Institute for Public Health, University of Calgary, Calgary, Alberta, Canada. ·Alzheimers Dement · Pubmed #31914223.

ABSTRACT: INTRODUCTION: Mild behavioral impairment (MBI) is characterized by the emergence of neuropsychiatric symptoms in elderly persons. Here, we examine the associations between MBI and Alzheimer's disease (AD) biomarkers in asymptomatic elderly individuals. METHODS: Ninety-six cognitively normal elderly individuals underwent MRI, [ RESULTS: Pearson correlations revealed a positive relationship between MBI-C score and global and striatal [ CONCLUSION: We demonstrate for the first time a link between MBI and early AD pathology in a cognitively intact elderly population, supporting the use of the MBI-C as a metric to enhance clinical trial enrolment.

2 Article Suicidal ideation is common in autosomal dominant Alzheimer's disease at-risk persons. 2020

Ng, Kok Pin / Richard-Devantoy, Stéphane / Bertrand, Josie-Anne / Jiang, Lai / Pascoal, Tharick A / Mathotaarachchi, Sulantha / Therriault, Joseph / Yatawara, Chathuri / Kandiah, Nagaendran / Greenwood, Celia M T / Rosa-Neto, Pedro / Gauthier, Serge / Anonymous861181. ·Alzheimer's Disease Research Unit, McGill Centre for Studies in Aging, McGill University, Québec, Canada. · Department of Neurology, National Neuroscience Institute, Singapore. · Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, Québec, Canada. · Department of Psychiatry & Douglas Mental Health University Institute, McGill Group for Suicide Studies, McGill University, Québec, Montréal, Canada. · CISSS des Laurentides, Quebec, Canada. · Douglas Research Center, Douglas Mental Health University Institute, Québec, Canada. · Lady Davis Institute, McGill University, Québec, Canada. · Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Québec, Canada. ·Int J Geriatr Psychiatry · Pubmed #31642105.

ABSTRACT: OBJECTIVES: To study the frequency of suicidal ideation and its association with clinical and neurobiological correlates among cognitively intact autosomal dominant Alzheimer's disease (ADAD) at-risk individuals. METHODS/DESIGN: In a cross-sectional study of 183 ADAD at-risk individuals (91 mutation carriers and 92 noncarriers), we compared the frequency of suicidal ideation among carriers and noncarriers. Linear mixed-effects models with family-level random effects evaluated the relationships between geriatric depression scale (GDS), neuropsychiatric inventory-questionnaire (NPI-Q), and suicidal ideation scores among all ADAD at-risk individuals. An interaction term was added to the regression models to evaluate the interactions of suicidal ideation and mutation status on neuropsychiatric symptoms. RESULTS: Twenty-six (14.20%) ADAD at-risk individuals (13 [14.28%] carriers and 13 [14.13%] noncarriers) had suicidal ideation. The frequency of suicidal ideation did not differ between carriers and noncarriers. Suicidal ideation was associated with higher GDS among all ADAD at-risk individuals. When stratified into mutation carrier status, noncarriers with suicidal ideation had higher GDS than carriers. There was no statistically significant association between suicidal ideation and NPI-Q among ADAD at-risk individuals. Awareness of mutation status, neuropsychological performances, and cerebrospinal fluid AD biomarkers were not associated with suicidal ideation among carriers and noncarriers. CONCLUSIONS: Suicidal ideation is common among cognitively intact ADAD at-risk individuals. While ADAD at-risk individuals with suicidal ideation have greater depressive symptoms, noncarriers with suicidal ideation have higher GDS scores than carriers. Interestingly, awareness of the mutation status was not associated with suicidal ideation in our study. Early identification of suicidal thoughts can facilitate timely interventions to prevent suicidal behaviours. Keywords autosomal dominant Alzheimer's diseasedominantly inherited Alzheimer's networkneuropsychiatric symptomssuicidal ideation.

3 Article Plasma neurofilament light associates with Alzheimer's disease metabolic decline in amyloid-positive individuals. 2019

Benedet, Andréa L / Ashton, Nicholas J / Pascoal, Tharick A / Leuzy, Antoine / Mathotaarachchi, Sulantha / Kang, Min S / Therriault, Joseph / Savard, Melissa / Chamoun, Mira / Schöll, Michael / Zimmer, Eduardo R / Gauthier, Serge / Labbe, Aurélie / Zetterberg, Henrik / Blennow, Kaj / Neto, Pedro R. ·Translational Neuroimaging Laboratory, McGill Centre for Studies in Aging, McGill University, Montreal, Quebec, Canada. · CAPES Foundation, Ministry of Education of Brazil, Brasília, Brazil. · Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden. · Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden. · King's College London, Institute of Psychiatry, Psychology and Neuroscience, Maurice Wohl Institute Clinical Neuroscience Institute, London, UK. · NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation, London, UK. · Clinical Memory Research Unit, Department of Clinical Sciences, Malmö, Lund University, Lund, Sweden. · Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK. · Alzheimer's Disease Research Unit, The McGill University Research Centre for Studies in Aging, Montreal, McGill University, Montreal, Quebec, Canada. · Department of Pharmacology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. · Department of Decision Sciences, HEC Montreal, Montreal, Quebec, Canada. · Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden. · Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK. · UK Dementia Research Institute at UCL, London, UK. · Montreal Neurological Institute, Montreal, Quebec, Canada. · Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada. ·Alzheimers Dement (Amst) · Pubmed #31673598.

ABSTRACT: Introduction: Neurofilament light chain (NfL) is a promising blood biomarker to detect neurodegeneration in Alzheimer's disease (AD) and other brain disorders. However, there are limited reports of how longitudinal NfL relates to imaging biomarkers. We herein investigated the relationship between blood NfL and brain metabolism in AD. Methods: Voxelwise regression models tested the cross-sectional association between [ Results: Higher concentrations of plasma and cerebrospinal fluid NfL were associated with reduced [ Discussion: These findings indicate that plasma NfL is a proxy for neurodegeneration in AD-related regions in Aβ+ subjects.

4 Article Non-invasive in vivo hyperspectral imaging of the retina for potential biomarker use in Alzheimer's disease. 2019

Hadoux, Xavier / Hui, Flora / Lim, Jeremiah K H / Masters, Colin L / Pébay, Alice / Chevalier, Sophie / Ha, Jason / Loi, Samantha / Fowler, Christopher J / Rowe, Christopher / Villemagne, Victor L / Taylor, Edward N / Fluke, Christopher / Soucy, Jean-Paul / Lesage, Frédéric / Sylvestre, Jean-Philippe / Rosa-Neto, Pedro / Mathotaarachchi, Sulantha / Gauthier, Serge / Nasreddine, Ziad S / Arbour, Jean Daniel / Rhéaume, Marc-André / Beaulieu, Sylvain / Dirani, Mohamed / Nguyen, Christine T O / Bui, Bang V / Williamson, Robert / Crowston, Jonathan G / van Wijngaarden, Peter. ·Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, 3002, VIC, Australia. xavier.hadoux@unimelb.edu.au. · Ophthalmology, Department of Surgery, University of Melbourne, Parkville, 3010, VIC, Australia. xavier.hadoux@unimelb.edu.au. · Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, 3002, VIC, Australia. · Ophthalmology, Department of Surgery, University of Melbourne, Parkville, 3010, VIC, Australia. · Department of Optometry and Vision Sciences, University of Melbourne, Parkville, 3010, VIC, Australia. · The Florey Institute, The University of Melbourne, Parkville, 3010, VIC, Australia. · Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, 3800, VIC, Australia. · Neuropsychiatry Unit, North Western Mental Health, Melbourne Health, Royal Melbourne Hospital, Parkville, 3050, VIC, Australia. · University of Melbourne, Department of Psychiatry, Parkville, 3010, VIC, Australia. · Austin Health, Melbourne, 3084, VIC, Australia. · Centre for Astrophysics and Supercomputing, Swinburne University of Technology, Melbourne, 3122, VIC, Australia. · OzGrav-Swinburne, Centre for Astrophysics & Supercomputing, Swinburne University of Technology, Melbourne, 3122, VIC, Australia. · Advanced Visualisation Laboratory, Digital Research Innovation Capability Platform, Swinburne University of Technology, Melbourne, 3122, VIC, Australia. · McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, H3A 2B4, QC, Canada. · PERFORM Centre, Concordia University, Montreal, H4B 1R6, QC, Canada. · École Polytechnique de Montréal, Institut de génie biomédical, Département de Génie électrique, Montreal, H3C 3A7, QC, Canada. · Research Center, Montreal Heart Institute, Montreal, H1T 1C8, QC, Canada. · Optina Diagnostics, Montreal, H4T 1Z2, QC, Canada. · Translational Neuroimaging Laboratory, McGill Centre for Studies in Aging, Douglas Mental Health University Institute, Montreal, H4H 1R3, QC, Canada. · Alzheimer's Disease Research Unit, The McGill University Research Centre for Studies in Aging, McGill University, Montreal, H4H 1R3, QC, Canada. · MoCA Clinic and Institute, Greenfield Park, J4V 2J2, QC, Canada. · Clinique ophtalmologique 2121, Montreal, H3H 1G6, QC, Canada. · Département de médecine nucléaire, Hôpital Maisonneuve-Rosemont, Montreal, H1T 2M4, QC, Canada. · Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, 169856, Singapore. · Murdoch Children's Research Institute and Department of Paediatrics, University of Melbourne, Melbourne, 3052, VIC, Australia. · Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, 3002, VIC, Australia. peterv@unimelb.edu.au. · Ophthalmology, Department of Surgery, University of Melbourne, Parkville, 3010, VIC, Australia. peterv@unimelb.edu.au. ·Nat Commun · Pubmed #31530809.

ABSTRACT: Studies of rodent models of Alzheimer's disease (AD) and of human tissues suggest that the retinal changes that occur in AD, including the accumulation of amyloid beta (Aβ), may serve as surrogate markers of brain Aβ levels. As Aβ has a wavelength-dependent effect on light scatter, we investigate the potential for in vivo retinal hyperspectral imaging to serve as a biomarker of brain Aβ. Significant differences in the retinal reflectance spectra are found between individuals with high Aβ burden on brain PET imaging and mild cognitive impairment (n = 15), and age-matched PET-negative controls (n = 20). Retinal imaging scores are correlated with brain Aβ loads. The findings are validated in an independent cohort, using a second hyperspectral camera. A similar spectral difference is found between control and 5xFAD transgenic mice that accumulate Aβ in the brain and retina. These findings indicate that retinal hyperspectral imaging may predict brain Aβ load.

5 Article Rostral-Caudal Hippocampal Functional Convergence Is Reduced Across the Alzheimer's Disease Spectrum. 2019

Therriault, Joseph / Wang, S / Mathotaarachchi, S / Pascoal, Tharick A / Parent, M / Beaudry, T / Shin, M / Al, Benedet / Kang, M S / Ng, K P / Dansereau, C / Park, M T M / Fonov, V / Carbonell, F / Zimmer, E / Chakravarty, M Mallar / Bellec, P / Gauthier, S / Rosa-Neto, P / Anonymous2081152. ·McGill University Research Centre for Studies in Aging, Douglas Mental Health University Institute, Montreal, Canada. joseph.therriault1@gmail.com. · Douglas Mental Health University Institute, Montreal, Canada. joseph.therriault1@gmail.com. · Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, Douglas Hospital, McGill University, 6875 La Salle Blvd - FBC room 3149, Montreal, QC, H4H 1R3, Canada. joseph.therriault1@gmail.com. · McGill University Research Centre for Studies in Aging, Douglas Mental Health University Institute, Montreal, Canada. · Douglas Mental Health University Institute, Montreal, Canada. · Institut universitaire de gériatrie de Montréal, Université de Montréal, Montreal, Canada. · McConnell Brain Imaging Centre, Montreal Neurological Institute, Montreal, Canada. · Brain Institute of Rio Grande do Sul, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, RS, 90619-900, Brazil. · Department of Neurology and Neurosurgery, McGill University, Montreal, Canada. ·Mol Neurobiol · Pubmed #31230260.

ABSTRACT: Beginning in the early stages of Alzheimer's disease (AD), the hippocampus reduces its functional connections to other cortical regions due to synaptic depletion. However, little is known regarding connectivity abnormalities within the hippocampus. Here, we describe rostral-caudal hippocampal convergence (rcHC), a metric of the overlap between the rostral and caudal hippocampal functional networks, across the clinical spectrum of AD. We predicted a decline in rostral-caudal hippocampal convergence in the early stages of the disease. Using fMRI, we generated resting-state hippocampal functional networks across 56 controls, 48 early MCI (EMCI), 35 late MCI (LMCI), and 31 AD patients from the Alzheimer's Disease Neuroimaging Initiative cohort. For each diagnostic group, we performed a conjunction analysis and compared the rostral and caudal hippocampal network changes using a mixed effects linear model to estimate the convergence and differences between these networks, respectively. The conjunction analysis showed a reduction of rostral-caudal hippocampal convergence strength from early MCI to AD, independent of hippocampal atrophy. Our results demonstrate a parallel between the functional convergence within the hippocampus and disease stage, which is independent of brain atrophy. These findings support the concept that network convergence might contribute as a biomarker for connectivity dysfunction in early stages of AD.

6 Article Aβ-induced vulnerability propagates via the brain's default mode network. 2019

Pascoal, Tharick A / Mathotaarachchi, Sulantha / Kang, Min Su / Mohaddes, Sara / Shin, Monica / Park, Ah Yeon / Parent, Maxime J / Benedet, Andrea L / Chamoun, Mira / Therriault, Joseph / Hwang, Heungsun / Cuello, A Claudio / Misic, Bratislav / Soucy, Jean-Paul / Aston, John A D / Gauthier, Serge / Rosa-Neto, Pedro. ·Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, H4H 1R3, Montreal, Canada. · Montreal Neurological Institute, H3A 2B4, Montreal, Canada. · Statistical Laboratory, University of Cambridge, CB3 0WB, Cambridge, UK. · Department of Psychology, McGill University, Montreal, Canada. · Department of Pharmacology and Therapeutics, McGill University, H3A 2T5, Montreal, Canada. · Alzheimer's Disease Research Unit, The McGill University Research Centre for Studies in Aging, H4H 1R3, Montreal, Canada. · Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, H4H 1R3, Montreal, Canada. pedro.rosa@mcgill.ca. · Montreal Neurological Institute, H3A 2B4, Montreal, Canada. pedro.rosa@mcgill.ca. · Department of Pharmacology and Therapeutics, McGill University, H3A 2T5, Montreal, Canada. pedro.rosa@mcgill.ca. · Alzheimer's Disease Research Unit, The McGill University Research Centre for Studies in Aging, H4H 1R3, Montreal, Canada. pedro.rosa@mcgill.ca. ·Nat Commun · Pubmed #31164641.

ABSTRACT: The link between brain amyloid-β (Aβ), metabolism, and dementia symptoms remains a pressing question in Alzheimer's disease. Here, using positron emission tomography ([

7 Article Regional Amyloid-β Load and White Matter Abnormalities Contribute to Hypometabolism in Alzheimer's Dementia. 2019

Schilling, Lucas Porcello / Pascoal, Tharick A / Zimmer, Eduardo R / Mathotaarachchi, Sulantha / Shin, Monica / de Mello Rieder, Carlos Roberto / Gauthier, Serge / Palmini, André / Rosa-Neto, Pedro / Anonymous441053. ·Translational Neuroimaging Laboratory (TNL), McGill Center for Studies in Aging (MCSA), Douglas Mental Health Research Institute, 6825, boul. LaSalle Blvd., Montréal, QC, H4H1R3, Canada. · Alzheimer's Disease Research Unit, MCSA, Douglas Mental Health Research Institute, Montréal, Canada. · Brain Institute of Rio Grande do Sul (BraIns), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil. · Department of Pharmacology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil. · Graduate Program in Biological Science: Biochemistry, UFRGS, Porto Alegre, Brazil. · Graduate Program in Biological Sciences: Pharmacology and Therapeutics, UFRGS, Porto Alegre, Brazil. · Translational Neuroimaging Laboratory (TNL), McGill Center for Studies in Aging (MCSA), Douglas Mental Health Research Institute, 6825, boul. LaSalle Blvd., Montréal, QC, H4H1R3, Canada. pedro.rosa@mcgill.ca. · Alzheimer's Disease Research Unit, MCSA, Douglas Mental Health Research Institute, Montréal, Canada. pedro.rosa@mcgill.ca. ·Mol Neurobiol · Pubmed #30414086.

ABSTRACT: We investigated the association between amyloid-β deposition and white matter (WM) integrity as a determinant of brain glucose hypometabolism across the Alzheimer's disease (AD) spectrum. We assessed ninety-six subjects (27 cognitively normal, 49 mild cognitive impairment, and 20 AD dementia) who underwent [

8 Article In vivo quantification of neurofibrillary tangles with [ 2018

Pascoal, Tharick A / Shin, Monica / Kang, Min Su / Chamoun, Mira / Chartrand, Daniel / Mathotaarachchi, Sulantha / Bennacef, Idriss / Therriault, Joseph / Ng, Kok Pin / Hopewell, Robert / Bouhachi, Reda / Hsiao, Hung-Hsin / Benedet, Andrea L / Soucy, Jean-Paul / Massarweh, Gassan / Gauthier, Serge / Rosa-Neto, Pedro. ·Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, 6825 LaSalle Boulevard, Verdun, QC, H4H 1R3, Canada. · Montreal Neurological Institute, 3801 University Street, Montreal, QC, H3A 2B4, Canada. · Translational Biomarkers, Merck & Co., Inc., 770 Sumneytown Pike, West Point, PA, 19486, USA. · Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, 6825 LaSalle Boulevard, Verdun, QC, H4H 1R3, Canada. pedro.rosa@mcgill.ca. · Montreal Neurological Institute, 3801 University Street, Montreal, QC, H3A 2B4, Canada. pedro.rosa@mcgill.ca. · Douglas Hospital, McGill University, 6875 La Salle Blvd-FBC room 3149, Montreal, QC, H4H 1R3, Canada. pedro.rosa@mcgill.ca. ·Alzheimers Res Ther · Pubmed #30064520.

ABSTRACT: BACKGROUND: Imaging agents capable of quantifying the brain's tau aggregates will allow a more precise staging of Alzheimer's disease (AD). The aim of the present study was to examine the in vitro properties as well as the in vivo kinetics, using gold standard methods, of the novel positron emission tomography (PET) tau imaging agent [ METHODS: In vitro properties of [ RESULTS: In vitro [ CONCLUSIONS: This evaluation shows an [

9 Article Amyloid and tau signatures of brain metabolic decline in preclinical Alzheimer's disease. 2018

Pascoal, Tharick A / Mathotaarachchi, Sulantha / Shin, Monica / Park, Ah Yeon / Mohades, Sara / Benedet, Andrea L / Kang, Min Su / Massarweh, Gassan / Soucy, Jean-Paul / Gauthier, Serge / Rosa-Neto, Pedro / Anonymous2190935. ·Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, Douglas Hospital, McGill University, 6875 La Salle Blvd - FBC room 3149, Montreal, QC, H4H 1R3, Canada. · Statistical Laboratory, University of Cambridge, Cambridge, UK. · Montreal Neurological Institute, Montreal, Canada. · PERFORM Centre, Concordia University, Montreal, Canada. · Alzheimer's Disease Research Unit, The McGill University Research Centre for Studies in Aging, Douglas Hospital, McGill University, Montreal, Canada. · Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, Douglas Hospital, McGill University, 6875 La Salle Blvd - FBC room 3149, Montreal, QC, H4H 1R3, Canada. pedro.rosa@mcgill.ca. · Montreal Neurological Institute, Montreal, Canada. pedro.rosa@mcgill.ca. · Alzheimer's Disease Research Unit, The McGill University Research Centre for Studies in Aging, Douglas Hospital, McGill University, Montreal, Canada. pedro.rosa@mcgill.ca. · Department of Neurology and Neurosurgery, McGill University, Montreal, Canada. pedro.rosa@mcgill.ca. ·Eur J Nucl Med Mol Imaging · Pubmed #29396637.

ABSTRACT: PURPOSE: We aimed to determine the amyloid (Aβ) and tau biomarker levels associated with imminent Alzheimer's disease (AD) - related metabolic decline in cognitively normal individuals. METHODS: A threshold analysis was performed in 120 cognitively normal elderly individuals by modelling 2-year declines in brain glucose metabolism measured with [ RESULTS: The combination of [ CONCLUSIONS: These results highlight the new concept that combined Aβ and tau thresholds can predict imminent neurodegeneration as an alternative framework with a high statistical power for testing the effect of disease-modifying therapies on [

10 Article Characterizing biomarker features of cognitively normal individuals with ventriculomegaly. 2018

Li, Xiaofeng / Ba, Maowen / Ng, Kok Pin / Mathotaarachchi, Sulantha / Pascoal, Tharick A / Rosa-Neto, Pedro / Gauthier, Serge. ·Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, PR China. · Alzheimer's Disease Research Unit, The McGill University Research Centre for Studies in Aging, McGill University, Montreal, Canada. · Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, Montreal, Canada. · Department of Neurology, Yantai Yuhuangding Hospital Affiliated to Qingdao Medical University, Shandong, PR China. · Department of Neurology, National Neuroscience Institute, Singapore, Singapore. ·Alzheimers Dement (Amst) · Pubmed #29159265.

ABSTRACT: Introduction: The clinical significance of ventriculomegaly in cognitively normal elderly individuals remains unclear. Methods: We selected cognitively normal individuals (n = 425) from the Alzheimer's Disease Neuroimaging Initiative database and calculated Evans index (EI) based on the ratio of the frontal horn and skull diameter. We defined ventriculomegaly as EI ≥ 0.30, and the participants were stratified into EI ≥ 0.30 group and EI < 0.30 group. Neuropsychological, imaging, and fluid biomarker profiles between the two groups were then compared using regression models. Results: A total of 96 (22.5%) individuals who had ventriculomegaly performed worse on the cognitive tests; showed smaller hippocampal volume but larger caudate, cingulate, and paracentral gyrus volumes; and displayed lower positron emission tomography [ Discussion: Asymptomatic ventriculomegaly might be an early imaging signature of preclinical Alzheimer's disease and/or normal pressure hydrocephalus.

11 Article Author response: Neuropsychiatric symptoms predict hypometabolism in preclinical Alzheimer disease. 2017

Gauthier, Serge / Ng, Kok Pin / Pascoal, Tharick A / Mathotaarachchi, Sulantha / Chung, Chang-Oh / Benedetti, Andréa L / Shin, Monica / Kang, Min Su / Li, Xiaofeng / Ba, Maowen / Kandiah, Nagaendran / Rosa-Neto, Pedro. ·Montreal. · Singapore. · Verdun, Canada. · Gwangju, Korea. · Chongqing. · Yantai, China. ·Neurology · Pubmed #29084927.

ABSTRACT: -- No abstract --

12 Article The prevalence and biomarkers' characteristic of rapidly progressive Alzheimer's disease from the Alzheimer's Disease Neuroimaging Initiative database. 2017

Ba, Maowen / Li, Xiaofeng / Ng, Kok Pin / Pascoal, Tharick A / Mathotaarachchi, Sulantha / Rosa-Neto, Pedro / Gauthier, Serge / Anonymous4260924. ·Department of Neurology, Yantai Yuhuangding Hospital Affiliated to Qingdao Medical University, Shandong, People's Republic of China. · Alzheimer's Disease Research Unit, McGill Centre for Studies in Aging, McGill University, Douglas Institute, Montreal, Quebec, Canada. · Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China. · Department of Neurology, National Neuroscience Institute, Singapore. ·Alzheimers Dement (N Y) · Pubmed #29067322.

ABSTRACT: INTRODUCTION: The prevalence and detailed biomarkers' characteristic of rapidly progressive Alzheimer's disease (rpAD) remain incompletely understood. METHODS: A total of 312 mild AD patients from the Alzheimer's Disease Neuroimaging Initiative database were chosen and dichotomized into rpAD and non-rpAD groups. We performed the prevalence and comprehensive biomarker evaluation. RESULTS: The prevalence of rpAD was 17.6% in mild AD. Compared with non-rpAD, there were no differences in DISCUSSION: We identified that rpAD commonly existed in mild AD. Cerebral hypometabolism could provide potential clinical differential value for rpAD in the short-term follow-up period.

13 Article Identifying incipient dementia individuals using machine learning and amyloid imaging. 2017

Mathotaarachchi, Sulantha / Pascoal, Tharick A / Shin, Monica / Benedet, Andrea L / Kang, Min Su / Beaudry, Thomas / Fonov, Vladimir S / Gauthier, Serge / Rosa-Neto, Pedro / Anonymous3620914. ·Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging (MCSA), Douglas Research Institute, McGill University, Montreal, Quebec, Canada; McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada. · Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging (MCSA), Douglas Research Institute, McGill University, Montreal, Quebec, Canada. · McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada. · McGill University Research Centre for Studies in Aging (MCSA), Douglas Research Institute, McGill University, Montreal, Quebec, Canada; Douglas Research Institute, McGill University, Montreal, Quebec, Canada; Department of Psychiatry, McGill University, Montreal, Quebec, Canada; Department of Neurology & Neurosurgery, McGill University, Montreal, Quebec, Canada. · Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging (MCSA), Douglas Research Institute, McGill University, Montreal, Quebec, Canada; McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada; McGill University Research Centre for Studies in Aging (MCSA), Douglas Research Institute, McGill University, Montreal, Quebec, Canada; Douglas Research Institute, McGill University, Montreal, Quebec, Canada; Department of Psychiatry, McGill University, Montreal, Quebec, Canada; Department of Neurology & Neurosurgery, McGill University, Montreal, Quebec, Canada. Electronic address: pedro.rosa@mcgill.ca. ·Neurobiol Aging · Pubmed #28756942.

ABSTRACT: Identifying individuals destined to develop Alzheimer's dementia within time frames acceptable for clinical trials constitutes an important challenge to design studies to test emerging disease-modifying therapies. Although amyloid-β protein is the core pathologic feature of Alzheimer's disease, biomarkers of neuronal degeneration are the only ones believed to provide satisfactory predictions of clinical progression within short time frames. Here, we propose a machine learning-based probabilistic method designed to assess the progression to dementia within 24 months, based on the regional information from a single amyloid positron emission tomography scan. Importantly, the proposed method was designed to overcome the inherent adverse imbalance proportions between stable and progressive mild cognitive impairment individuals within a short observation period. The novel algorithm obtained an accuracy of 84% and an under-receiver operating characteristic curve of 0.91, outperforming the existing algorithms using the same biomarker measures and previous studies using multiple biomarker modalities. With its high accuracy, this algorithm has immediate applications for population enrichment in clinical trials designed to test disease-modifying therapies aiming to mitigate the progression to Alzheimer's disease dementia.

14 Article Neuropsychiatric symptoms predict hypometabolism in preclinical Alzheimer disease. 2017

Ng, Kok Pin / Pascoal, Tharick A / Mathotaarachchi, Sulantha / Chung, Chang-Oh / Benedet, Andréa L / Shin, Monica / Kang, Min Su / Li, Xiaofeng / Ba, Maowen / Kandiah, Nagaendran / Rosa-Neto, Pedro / Gauthier, Serge / Anonymous1420903. ·From the Translational Neuroimaging Laboratory (K.P.N., T.A.P., S.M., C.-O.C., A.L.B., M.S., M.S.K., P.R.-N.) and Alzheimer's Disease Research Unit (K.P.N., X.L., M.B., P.R.-N., S.G.), McGill University Research Centre for Studies in Aging, Montreal, Quebec, Canada · Department of Neurology (K.P.N., N.K.), National Neuroscience Institute, Singapore · Montreal Neurological Institute (P.R.-N.) · Department of Neurology and Neurosurgery (P.R.-N.), McGill University, Montreal, Quebec, Canada · Department of Neurology (X.L.), The Second Affiliated Hospital of Chongqing Medical University, Chongqing · and Department of Neurology (M.B.), Yantai Yuhuangding Hospital Affiliated to Qingdao Medical University, Shandong, PR China. ·Neurology · Pubmed #28404803.

ABSTRACT: OBJECTIVE: To identify regional brain metabolic dysfunctions associated with neuropsychiatric symptoms (NPS) in preclinical Alzheimer disease (AD). METHODS: We stratified 115 cognitively normal individuals into preclinical AD (both amyloid and tau pathologies present), asymptomatic at risk for AD (either amyloid or tau pathology present), or healthy controls (no amyloid or tau pathology present) using [ RESULTS: Individuals with preclinical AD with higher NPI scores had higher [ CONCLUSIONS: The magnitude of NPS in preclinical cases, driven by sleep behavior and irritability domains, is linked to transitory metabolic dysfunctions within limbic networks vulnerable to the AD process and predicts subsequent PCC hypometabolism. These findings support an emerging conceptual framework in which NPS constitute an early clinical manifestation of AD pathophysiology.

15 Article Monoamine oxidase B inhibitor, selegiline, reduces 2017

Ng, Kok Pin / Pascoal, Tharick A / Mathotaarachchi, Sulantha / Therriault, Joseph / Kang, Min Su / Shin, Monica / Guiot, Marie-Christine / Guo, Qi / Harada, Ryuichi / Comley, Robert A / Massarweh, Gassan / Soucy, Jean-Paul / Okamura, Nobuyuki / Gauthier, Serge / Rosa-Neto, Pedro. ·Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, 6825 LaSalle Boulevard, Verdun, Québec, H4H 1R3, Canada. · Department of Neurology, National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore, 308433, Singapore. · Alzheimer's Disease Research Unit, The McGill University Research Centre for Studies in Aging, McGill University, 6825 LaSalle Boulevard, Verdun, Québec, H4H 1R3, Canada. · Montreal Neurological Institute/Hospital, Department of Pathology, McGill University Hospital Centre, 3801 University Street, Montreal, Québec, H3A 2B4, Canada. · AbbVie Inc., 1 North Waukegan Road, North Chicago, IL, USA. · Department of Pharmacology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan. · McConnell Brain Imaging Centre, McGill University, 3801 University Street, Montreal, Québec, H3A 2B4, Canada. · Division of Pharmacology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai, 981-8558, Japan. · Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, 6825 LaSalle Boulevard, Verdun, Québec, H4H 1R3, Canada. pedro.rosa@mcgill.ca. · Alzheimer's Disease Research Unit, The McGill University Research Centre for Studies in Aging, McGill University, 6825 LaSalle Boulevard, Verdun, Québec, H4H 1R3, Canada. pedro.rosa@mcgill.ca. · Montreal Neurological Institute, 3801 University Street, Montreal, Québec, H3A 2B4, Canada. pedro.rosa@mcgill.ca. · Department of Neurology and Neurosurgery, McGill University, 3801 University Street, Montreal, Québec, H3A 2B4, Canada. pedro.rosa@mcgill.ca. ·Alzheimers Res Ther · Pubmed #28359327.

ABSTRACT: METHODS: Eight participants (five mild cognitive impairment, two Alzheimer's disease, and one progressive supranuclear palsy) had baseline RESULTS: At baseline, CONCLUSIONS: These results indicate that the interpretation of

16 Article Synergistic interaction between amyloid and tau predicts the progression to dementia. 2017

Pascoal, Tharick A / Mathotaarachchi, Sulantha / Shin, Monica / Benedet, Andrea L / Mohades, Sara / Wang, Seqian / Beaudry, Tom / Kang, Min Su / Soucy, Jean-Paul / Labbe, Aurelie / Gauthier, Serge / Rosa-Neto, Pedro / Anonymous4620891. ·Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, Montreal, Canada. · Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, Montreal, Canada; CAPES Foundation, Ministry of Education of Brazil, Brasília, Brazil. · Montreal Neurological Institute, Montreal, Canada. · Douglas Hospital Research Centre, McGill University, Montreal, Canada; Department of Epidemiology, Biostatistics & Occupational Health, McGill University, Montreal, Canada. · AD Research Unit, The McGill University Research Centre for Studies in Aging, Montreal, Canada; McGill University, Montreal, Canada. · Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, Montreal, Canada; Montreal Neurological Institute, Montreal, Canada; AD Research Unit, The McGill University Research Centre for Studies in Aging, Montreal, Canada; McGill University, Montreal, Canada; Department of Neurology and Neurosurgery, McGill University, Montreal, Canada. Electronic address: pedro.rosa@mcgill.ca. ·Alzheimers Dement · Pubmed #28024995.

ABSTRACT: INTRODUCTION: Recent literature proposes that amyloid β (Aβ) and phosphorylated tau (p-tau) synergism accelerates biomarker abnormalities in controls. Yet, it remains to be answered whether this synergism is the driving force behind Alzheimer disease (AD) dementia. METHODS: We stratified 314 mild cognitive impairment individuals using [ RESULTS: We found that the synergism between [ DISCUSSION: Together, the present results support that progression to AD dementia is driven by the synergistic rather than a mere additive effect between Aβ and p-tau proteins.

17 Article Amyloid-β and hyperphosphorylated tau synergy drives metabolic decline in preclinical Alzheimer's disease. 2017

Pascoal, T A / Mathotaarachchi, S / Mohades, S / Benedet, A L / Chung, C-O / Shin, M / Wang, S / Beaudry, T / Kang, M S / Soucy, J-P / Labbe, A / Gauthier, S / Rosa-Neto, P. ·Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, Douglas Hospital, McGill University, Montreal, QC, Canada. · CAPES Foundation, Ministry of Education of Brazil, Brasília, Brazil. · Montreal Neurological Institute, Montreal, QC, Canada. · Douglas Hospital Research Centre, McGill University, Montreal, QC, Canada. · Department of Epidemiology, Biostatistics & Occupational Health, McGill University, Montreal, QC, Canada. · Department of Psychiatry, McGill University Faculty of Medicine, Montreal, QC, Canada. · Alzheimer's Disease Research Unit, The McGill University Research Centre for Studies in Aging, Montreal, McGill University, Montreal, QC, Canada. · Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada. ·Mol Psychiatry · Pubmed #27021814.

ABSTRACT: This study was designed to test the interaction between amyloid-β and tau proteins as a determinant of metabolic decline in preclinical Alzheimer's disease (AD). We assessed 120 cognitively normal individuals with [

18 Article VoxelStats: A MATLAB Package for Multi-Modal Voxel-Wise Brain Image Analysis. 2016

Mathotaarachchi, Sulantha / Wang, Seqian / Shin, Monica / Pascoal, Tharick A / Benedet, Andrea L / Kang, Min Su / Beaudry, Thomas / Fonov, Vladimir S / Gauthier, Serge / Labbe, Aurélie / Rosa-Neto, Pedro. ·Translational Neuroimaging Laboratory, Departments of Neurology and Neurosurgery, McGill University Research Centre for Studies in Aging, Douglas Research Institute, McGill UniversityMontreal, QC, Canada; McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill UniversityMontreal, QC, Canada. · Translational Neuroimaging Laboratory, Departments of Neurology and Neurosurgery, McGill University Research Centre for Studies in Aging, Douglas Research Institute, McGill University Montreal, QC, Canada. · McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University Montreal, QC, Canada. · McGill University Research Centre for Studies in Aging, Douglas Research Institute, McGill UniversityMontreal, QC, Canada; Douglas Hospital Research Center, Douglas Research Institute, McGill UniversityMontreal, QC, Canada; Department of Psychiatry, McGill UniversityMontreal, QC, Canada; Department of Neurology and Neurosurgery, McGill UniversityMontreal, QC, Canada. · Douglas Hospital Research Center, Douglas Research Institute, McGill UniversityMontreal, QC, Canada; Department of Psychiatry, McGill UniversityMontreal, QC, Canada; Department of Epidemiology and Biostatistics, McGill UniversityMontreal, QC, Canada. · Translational Neuroimaging Laboratory, Departments of Neurology and Neurosurgery, McGill University Research Centre for Studies in Aging, Douglas Research Institute, McGill UniversityMontreal, QC, Canada; McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill UniversityMontreal, QC, Canada; McGill University Research Centre for Studies in Aging, Douglas Research Institute, McGill UniversityMontreal, QC, Canada; Douglas Hospital Research Center, Douglas Research Institute, McGill UniversityMontreal, QC, Canada; Department of Psychiatry, McGill UniversityMontreal, QC, Canada; Department of Neurology and Neurosurgery, McGill UniversityMontreal, QC, Canada. ·Front Neuroinform · Pubmed #27378902.

ABSTRACT: In healthy individuals, behavioral outcomes are highly associated with the variability on brain regional structure or neurochemical phenotypes. Similarly, in the context of neurodegenerative conditions, neuroimaging reveals that cognitive decline is linked to the magnitude of atrophy, neurochemical declines, or concentrations of abnormal protein aggregates across brain regions. However, modeling the effects of multiple regional abnormalities as determinants of cognitive decline at the voxel level remains largely unexplored by multimodal imaging research, given the high computational cost of estimating regression models for every single voxel from various imaging modalities. VoxelStats is a voxel-wise computational framework to overcome these computational limitations and to perform statistical operations on multiple scalar variables and imaging modalities at the voxel level. VoxelStats package has been developed in Matlab(®) and supports imaging formats such as Nifti-1, ANALYZE, and MINC v2. Prebuilt functions in VoxelStats enable the user to perform voxel-wise general and generalized linear models and mixed effect models with multiple volumetric covariates. Importantly, VoxelStats can recognize scalar values or image volumes as response variables and can accommodate volumetric statistical covariates as well as their interaction effects with other variables. Furthermore, this package includes built-in functionality to perform voxel-wise receiver operating characteristic analysis and paired and unpaired group contrast analysis. Validation of VoxelStats was conducted by comparing the linear regression functionality with existing toolboxes such as glim_image and RMINC. The validation results were identical to existing methods and the additional functionality was demonstrated by generating feature case assessments (t-statistics, odds ratio, and true positive rate maps). In summary, VoxelStats expands the current methods for multimodal imaging analysis by allowing the estimation of advanced regional association metrics at the voxel level.

19 Article Epistasis analysis links immune cascades and cerebral amyloidosis. 2015

Benedet, Andréa L / Labbe, Aurélie / Lemay, Philippe / Zimmer, Eduardo R / Pascoal, Tharick A / Leuzy, Antoine / Mathotaarachchi, Sulantha / Mohades, Sara / Shin, Monica / Dionne-Laporte, Alexandre / Beaudry, Thomas / Picard, Cynthia / Gauthier, Serge / Poirier, Judes / Rouleau, Guy / Rosa-Neto, Pedro / Anonymous5120850. ·Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, 6825 LaSalle Blvd, H4H 1R3, Montreal, QC, Canada. andrea.benedet@mail.mcgill.ca. · CAPES Foundation, Ministry of Education of Brazil, Brasília, Brazil. andrea.benedet@mail.mcgill.ca. · Douglas Hospital Research Centre, McGill University, Montreal, Canada. aurelie.labbe@mcgill.ca. · Department of Epidemiology, Biostatistics & Occupational Health, McGill University, Montreal, Canada. aurelie.labbe@mcgill.ca. · Department of Psychiatry, McGill University, Montreal, Canada. aurelie.labbe@mcgill.ca. · Department of Biochemistry, Université de Montréal, Montréal, Canada. lemayph@gmail.com. · Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, 6825 LaSalle Blvd, H4H 1R3, Montreal, QC, Canada. erzimmer@gmail.com. · Department of Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, Brazil. erzimmer@gmail.com. · Brain Institute of Rio Grande do Sul (BraIns), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil. erzimmer@gmail.com. · Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, 6825 LaSalle Blvd, H4H 1R3, Montreal, QC, Canada. tharick.alipascoal@mail.mcgill.ca. · Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, 6825 LaSalle Blvd, H4H 1R3, Montreal, QC, Canada. antoine.leuzy@ki.se. · Department of NVS, Center for Alzheimer Research, Translational Alzheimer Neurobiology, Karolinska Institutet, Stockholm, Sweden. antoine.leuzy@ki.se. · Alzheimer's Disease Research Unit, McGill University Research Centre for Studies in Aging, McGill University, Montreal, Canada. antoine.leuzy@ki.se. · Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, 6825 LaSalle Blvd, H4H 1R3, Montreal, QC, Canada. mathotaarachchi.mathotaarachchi@mail.mcgill.ca. · Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, 6825 LaSalle Blvd, H4H 1R3, Montreal, QC, Canada. sara.mohades@gmail.com. · Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, 6825 LaSalle Blvd, H4H 1R3, Montreal, QC, Canada. monica.shin@mail.mcgill.ca. · Department of Neurology and Neurosurgery, McGill University, Montreal, Canada. alexandre.dionne-laporte@mcgill.ca. · Montreal Neurological Institute, Montreal, Canada. alexandre.dionne-laporte@mcgill.ca. · Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, 6825 LaSalle Blvd, H4H 1R3, Montreal, QC, Canada. waveflux@gmail.com. · Douglas Hospital Research Centre, McGill University, Montreal, Canada. cynthia.picard@mail.mcgill.ca. · Department of Neurology and Neurosurgery, McGill University, Montreal, Canada. serge.gauthier@mcgill.ca. · Douglas Hospital Research Centre, McGill University, Montreal, Canada. judes.poirier@mcgill.ca. · Alzheimer's Disease Research Unit, McGill University Research Centre for Studies in Aging, McGill University, Montreal, Canada. judes.poirier@mcgill.ca. · Department of Neurology and Neurosurgery, McGill University, Montreal, Canada. judes.poirier@mcgill.ca. · Department of Neurology and Neurosurgery, McGill University, Montreal, Canada. guy.rouleau@mcgill.ca. · Montreal Neurological Institute, Montreal, Canada. guy.rouleau@mcgill.ca. · Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, 6825 LaSalle Blvd, H4H 1R3, Montreal, QC, Canada. pedro.rosa@mcgill.ca. · Alzheimer's Disease Research Unit, McGill University Research Centre for Studies in Aging, McGill University, Montreal, Canada. pedro.rosa@mcgill.ca. · Department of Neurology and Neurosurgery, McGill University, Montreal, Canada. pedro.rosa@mcgill.ca. · Montreal Neurological Institute, Montreal, Canada. pedro.rosa@mcgill.ca. ·J Neuroinflammation · Pubmed #26626881.

ABSTRACT: BACKGROUND: Several lines of evidence suggest the involvement of neuroinflammatory changes in Alzheimer's disease (AD) pathophysiology such as amyloidosis and neurodegeneration. In fact, genome-wide association studies (GWAS) have shown a link between genes involved in neuroinflammation and AD. In order to further investigate whether interactions between candidate genetic variances coding for neuroinflammatory molecules are associated with brain amyloid β (Aβ) fibrillary accumulation, we conducted an epistasis analysis on a pool of genes associated with molecular mediators of inflammation. METHODS: [(18)F]Florbetapir positron emission tomography (PET) imaging was employed to assess brain Aβ levels in 417 participants from ADNI-GO/2 and posteriorly 174 from ADNI-1. IL-1β, IL4, IL6, IL6r, IL10, IL12, IL18, C5, and C9 genes were chosen based on previous studies conducted in AD patients. Using the [(18)F]florbetapir standardized uptake value ratio (SUVR) as a quantitative measure of fibrillary Aβ, epistasis analyses were performed between two sets of markers of immune-related genes using gender, diagnosis, and apolipoprotein E (APOE) as covariates. Voxel-based analyses were also conducted. The results were corrected for multiple comparison tests. Cerebrospinal fluid (CSF) Aβ1-42/phosphorylated tau (p-tau) ratio concentrations were used to confirm such associations. RESULTS: Epistasis analysis unveiled two significant single nucleotide polymorphism (SNP)-SNP interactions (false discovery rate (FDR) threshold 0.1), both interactions between C9 gene (rs261752) and IL6r gene (rs4240872, rs7514452). In a combined sample, the interactions were confirmed (p ≤ 10-5) and associated with amyloid accumulation within cognitively normal and AD spectrum groups. Voxel-based analysis corroborated initial findings. CSF biomarker (Aβ1-42/p-tau) confirmed the genetic interaction. Additionally, rs4240872 and rs7514452 SNPs were shown to be associated with CSF and plasma concentrations of IL6r protein. CONCLUSIONS: Certain allele combinations involving IL6r and C9 genes are associated with Aβ burden in the brain. Hypothesis-driven search for epistasis is a valuable strategy for investigating imaging endophenotypes in complex neurodegenerative diseases.