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Alzheimer Disease: HELP
Articles from NIH Bethesda
Based on 353 articles published since 2010
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These are the 353 published articles about Alzheimer Disease that originated from NIH Bethesda during 2010-2020.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6 · 7 · 8 · 9 · 10 · 11 · 12 · 13 · 14 · 15
1 Guideline Guidelines to improve animal study design and reproducibility for Alzheimer's disease and related dementias: For funders and researchers. 2016

Snyder, Heather M / Shineman, Diana W / Friedman, Lauren G / Hendrix, James A / Khachaturian, Ara / Le Guillou, Ian / Pickett, James / Refolo, Lorenzo / Sancho, Rosa M / Ridley, Simon H. ·Division of Medical & Scientific Relations, Alzheimer's Association, Chicago, IL, USA. Electronic address: hsnyder@alz.org. · Scientific Affairs, Alzheimer's Drug Discovery Foundation, New York, NY, USA. · Division of Medical & Scientific Relations, Alzheimer's Association, Chicago, IL, USA. · Editorial Office, Alzheimer's & Dementia: The Journal of the Alzheimer's Association, Washington, DC, USA. · Research Division, Alzheimer's Society, London, UK. · Division of Neuroscience, National Institute on Aging at the National Institutes of Health, Bethesda, MD, USA. · Research Division, Alzheimer's Research UK, Cambridge, UK. ·Alzheimers Dement · Pubmed #27836053.

ABSTRACT: The reproducibility of laboratory experiments is fundamental to the scientific process. There have been increasing reports regarding challenges in reproducing and translating preclinical experiments in animal models. In Alzheimer's disease and related dementias, there have been similar reports and growing interest from funding organizations, researchers, and the broader scientific community to set parameters around experimental design, statistical power, and reporting requirements. A number of efforts in recent years have attempted to develop standard guidelines; however, these have not yet been widely implemented by researchers or by funding agencies. A workgroup of the International Alzheimer's disease Research Funder Consortium, a group of over 30 research funding agencies from around the world, worked to compile the best practices identified in these prior efforts for preclinical biomedical research. This article represents a consensus of this work group's review and includes recommendations for researchers and funding agencies on designing, performing, reviewing, and funding preclinical research studies.

2 Guideline Recommendations of the Alzheimer's disease-related dementias conference. 2014

Montine, Thomas J / Koroshetz, Walter J / Babcock, Debra / Dickson, Dennis W / Galpern, Wendy R / Glymour, M Maria / Greenberg, Steven M / Hutton, Michael L / Knopman, David S / Kuzmichev, Andrey N / Manly, Jennifer J / Marder, Karen S / Miller, Bruce L / Phelps, Creighton H / Seeley, William W / Sieber, Beth-Anne / Silverberg, Nina B / Sutherland, Margaret / Torborg, Christine L / Waddy, Salina P / Zlokovic, Berislav V / Corriveau, Roderick A / Anonymous970802. ·From the Department of Pathology (T.J.M.), University of Washington, Seattle · National Institute of Neurological Disorders and Stroke (W.J.K., D.B., W.R.G., A.N.K., B.-A.S., M.S., C.L.T., S.P.W., R.A.C.), Bethesda, MD · Neuropathology Lab (D.W.D.), Mayo Clinic, Jacksonville, FL · Department of Epidemiology & Biostatistics (M.M.G.), University of California San Francisco · Hemorrhagic Stroke Research Program (S.M.G.), Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA · Neurodegenerative Diseases DHT at Eli Lilly and Company (M.L.H.), Lilly Research Center, Windlesham, UK · Department of Neurology (D.S.K.), Mayo Clinic Rochester, MN · Taub Institute for Research on Alzheimer's Disease and the Aging Brain (J.J.M., K.S.M.), Columbia University Medical Center, New York · Columbia University (J.J.M., K.S.M.), College of Physicians and Surgeons, New York, NY · University of California San Francisco Memory and Aging Center (B.L.M., W.W.S.) · National Institute on Aging (C.H.P., N.B.S.), Bethesda, MD · and Zilhka Neurogenetic Institute (B.V.Z.), Center for Neurodegeneration and Regeneration and Department of Physiology and Biophysics, University of Southern California, Keck School of Medicine, Los Angeles, CA. ·Neurology · Pubmed #25080517.

ABSTRACT: The National Alzheimer's Project Act, signed into law in 2011, mandates a National Plan to Address Alzheimer's Disease that is updated annually. In the Plan, the term Alzheimer disease includes not only Alzheimer disease (AD) proper, but also several specified related dementias, namely, frontotemporal, Lewy body, vascular, and mixed dementia. In response to a specific action item in the 2012 National Plan, the National Institute of Neurological Disorders and Stroke, in collaboration with the National Institute on Aging, convened panels of experts and conducted a 2-day public conference to develop research priorities and timelines for addressing Alzheimer disease-related dementias (ADRD) in 5 topic areas: multiple etiology dementias, health disparities, Lewy body dementias including dementia with Lewy bodies and Parkinson disease dementia, frontotemporal dementia and related tauopathies, and vascular contributions to ADRD. By design, the product was up to 8 prioritized research recommendations in each topic area including estimated timelines from when work on a recommendation is started to completion or to full implementation of an ongoing activity, and recognition of shared research themes across recommendations. These included increased education and training of both researchers and health care professionals, addressing health disparities, fundamental neurobiology research, advanced diagnostics, collaborative biosample repositories, and a focus on developing effective interventions to prevent or treat ADRD by the year 2025 as targeted by the National Plan.

3 Editorial Changing utilization of cardiovascular drugs during the course of Alzheimer's disease. 2020

Cermakova, Pavla. ·National Institute of Mental Health, Klecany, Czech Republic; Third Faculty of Medicine, Charles University Prague, Czech Republic. Electronic address: Pavla.Cermakova@nudz.cz. ·Int J Cardiol · Pubmed #31806282.

ABSTRACT: -- No abstract --

4 Editorial "Alzheimer's disease" is neither "Alzheimer's clinical syndrome" nor "dementia". 2019

Jagust, William / Jack, Clifford R / Bennett, David A / Blennow, Kaj / Haeberlein, Samantha Budd / Holtzman, David M / Jessen, Frank / Karlawish, Jason / Liu, Enchi / Molinuevo, Jose Luis / Montine, Thomas / Phelps, Creighton / Rankin, Katherine P / Rowe, Christopher C / Scheltens, Philip / Siemers, Eric / Sperling, Reisa. ·Helen Wills Neuroscience Institute, University of California, Berkeley, CA, USA. Electronic address: jagust@berkeley.edu. · Department of Radiology, Mayo Clinic, Rochester, MN, USA. · Department of Neurological Sciences, Rush University, Chicago, IL, USA. · Department of Psychiatry and Neurochemistry, University of Gothenburg, Gothenburg, Sweden. · Biogen, Cambridge, MA, USA. · Department of Neurology, Washington University, St. Louis, MO, USA. · Department of Psychiatry, University of Cologne, Medical Faculty, Cologne, Germany. · Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA. · Prothena Biosciences, Inc, South San Francisco, CA, USA. · BarcelonaBeta Brain Research Center, Pasqual Maragall Foundation and Hospital Clinic-IDIBAPS, Barcelona, Spain. · Department of Pathology, Stanford University, Stanford, CA, USA. · Formerly at National Institute on Aging, Bethesda, MD, USA. · Department of Neurology, University of California San Francisco, San Francisco, CA, USA. · Department of Molecular Imaging, Austin Health, University of Melbourne, Melbourne, Australia. · Department of Neurology, VU University Medical Center, Amsterdam, Netherlands. · Formerly at Eli Lilly and Company, Indianapolis, IN, USA. · Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA. ·Alzheimers Dement · Pubmed #30642435.

ABSTRACT: -- No abstract --

5 Editorial NIA commentary on the NIA-AA Research Framework: Towards a biological definition of Alzheimer's disease. 2018

Silverberg, Nina / Elliott, Cerise / Ryan, Laurie / Masliah, Eliezer / Hodes, Richard. ·National Institute on Aging, National Institutes of Health, Bethesda, MD, USA. · National Institute on Aging, National Institutes of Health, Bethesda, MD, USA. Electronic address: eliezer.masliah@nih.gov. ·Alzheimers Dement · Pubmed #29653608.

ABSTRACT: -- No abstract --

6 Editorial Twenty-First Century Diseases: Commonly Rare and Rarely Common? 2017

Daunert, Sylvia / Sittampalam, Gurusingham Sitta / Goldschmidt-Clermont, Pascal J. ·1 Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami , Miami, Florida. · 2 National Center for Advancing Translational Sciences, National Institutes of Health , Bethesda, Maryland. · 3 Department of Medicine, Cardiology Division, and Strategic International Projects, Miller School of Medicine, University of Miami , Miami, Florida. ·Antioxid Redox Signal · Pubmed #28482684.

ABSTRACT: Alzheimer's drugs are failing at a rate of 99.6%, and success rate for drugs designed to help patients with this form of dementia is 47 times less than for drugs designed to help patients with cancers ( www.scientificamerican.com/article/why-alzheimer-s-drugs-keep-failing/2014 ). How can it be so difficult to produce a valuable drug for Alzheimer's disease? Each human has a unique genetic and epigenetic makeup, thus endowing individuals with a highly unique complement of genes, polymorphisms, mutations, RNAs, proteins, lipids, and complex sugars, resulting in distinct genome, proteome, metabolome, and also microbiome identity. This editorial is taking into account the uniqueness of each individual and surrounding environment, and stresses the point that a more accurate definition of a "common" disorder could be simply the amalgamation of a myriad of "rare" diseases. These rare diseases are being grouped together because they share a rather constant complement of common features and, indeed, generally respond to empirically developed treatments, leading to a positive outcome consistently. We make the case that it is highly unlikely that such treatments, despite their statistical success measured with large cohorts using standardized clinical research, will be effective on all patients until we increase the depth and fidelity of our understanding of the individual "rare" diseases that are grouped together in the "buckets" of common illnesses. Antioxid. Redox Signal. 27, 511-516.

7 Editorial The crisis in recruitment for clinical trials in Alzheimer's and dementia: An action plan for solutions. 2016

Fargo, Keith N / Carrillo, Maria C / Weiner, Michael W / Potter, William Z / Khachaturian, Zaven. ·Alzheimer's Association, Chicago, IL, USA. · Center for Imaging of Neurodegenerative Diseases, San Francisco VA Medical Center, San Francisco, CA, USA. · National Institute of Mental Health (NIMH), Bethesda, MD, USA. · Alzheimer's & Dementia: The Journal of the Alzheimer's Association, Rockville, MD, USA. Electronic address: zaven@kra.net. ·Alzheimers Dement · Pubmed #27836052.

ABSTRACT: -- No abstract --

8 Editorial Accelerating Medicines Partnership: Alzheimer's Disease (AMP-AD) Knowledge Portal Aids Alzheimer's Drug Discovery through Open Data Sharing. 2016

Hodes, Richard J / Buckholtz, Neil. ·a National Institute on Aging , National Institutes of Health , Bethesda , MD , USA. ·Expert Opin Ther Targets · Pubmed #26853544.

ABSTRACT: -- No abstract --

9 Editorial Massachusetts Alzheimer's Disease Research Center: progress and challenges. 2015

Hyman, Bradley T / Growdon, John H / Albers, Mark W / Buckner, Randy L / Chhatwal, Jasmeer / Gomez-Isla, Maria Teresa / Haass, Christian / Hudry, Eloise / Jack, Clifford R / Johnson, Keith A / Khachaturian, Zaven S / Kim, Doo Yeon / Martin, Joseph B / Nitsch, Roger M / Rosen, Bruce R / Selkoe, Dennis J / Sperling, Reisa A / St George-Hyslop, Peter / Tanzi, Rudolph E / Yap, Liang / Young, Anne B / Phelps, Creighton H / McCaffrey, Patricia G. ·Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. Electronic address: bhyman@mgh.harvard.edu. · Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. · Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. · Department of Biochemistry, Ludwig-Maximilians-University, Munich, Bavaria, Germany. · Department of Radiology, Mayo Clinic, Rochester, MN, USA. · Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. · Khachaturian & Associates Inc, Potomac, MD, USA. · Department of Neurobiology, Harvard Medical School, Boston, MA, USA. · Department of Psychiatry, University of Zurich, Zurich, Switzerland. · Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. · Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. · Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. · Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK; Department of Medicine, University of Toronto, Toronto, Ontario, Canada. · National Institute on Aging, National Institutes of Health, Bethesda, MD, USA. · Freelance Science Writer, Newton, MA, USA. ·Alzheimers Dement · Pubmed #26297855.

ABSTRACT: -- No abstract --

10 Editorial Exploring the epigenetics of Alzheimer disease. 2015

Traynor, Bryan J / Renton, Alan E. ·Neuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland2Department of Neurology, The Johns Hopkins School of Medicine, Baltimore, Maryland. · Neuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland. ·JAMA Neurol · Pubmed #25365705.

ABSTRACT: -- No abstract --

11 Review Involvement of organelles and inter-organellar signaling in the pathogenesis of HIV-1 associated neurocognitive disorder and Alzheimer's disease. 2019

Khan, Nabab / Haughey, Norman J / Nath, Avindra / Geiger, Jonathan D. ·Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58203, United States. · Department of Neurology, Johns Hopkins University, Baltimore, MD, United States. · National Institute of Neurological Diseases and Stroke, Bethesda, MD, United States. · Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58203, United States. Electronic address: jonathan.geiger@und.edu. ·Brain Res · Pubmed #31425679.

ABSTRACT: Endolysosomes, mitochondria, peroxisomes, endoplasmic reticulum, and plasma membranes are now known to physically and functionally interact with each other. Such findings of inter-organellar signaling and communication has led to a resurgent interest in cell biology and an increased appreciation for the physiological actions and pathological consequences of the dynamic physical and chemical communications occurring between intracellular organelles. Others and we have shown that HIV-1 proteins implicated in the pathogenesis of neuroHIV and that Alzheimer's disease both affects the structure and function of intracellular organelles. Intracellular organelles are highly mobile, and their intracellular distribution almost certainly affects their ability to interact with other organelles and to regulate such important physiological functions as endolysosome acidification, cell motility, and nutrient homeostasis. Indeed, compounds that acidify endolysosomes cause endolysosomes to exhibit a mainly perinuclear pattern while compounds that de-acidify endolysosomes cause these organelles to exhibit a larger profile as well as movement towards plasma membranes. Endolysosome pH might be an early event in the pathogenesis of neuroHIV and Alzheimer's disease and in terms of organellar biology endolysosome changes might be upstream of HIV-1 protein-induced changes to other organelles. Thus, inter-organellar signaling mechanisms might be involved in the pathogenesis of neuroHIV and other neurological disorders, and a better understanding of inter-organellar signaling might lead to improved therapeutic strategies.

12 Review Version 3 of the National Alzheimer's Coordinating Center's Uniform Data Set. 2018

Besser, Lilah / Kukull, Walter / Knopman, David S / Chui, Helena / Galasko, Douglas / Weintraub, Sandra / Jicha, Gregory / Carlsson, Cynthia / Burns, Jeffrey / Quinn, Joseph / Sweet, Robert A / Rascovsky, Katya / Teylan, Merilee / Beekly, Duane / Thomas, George / Bollenbeck, Mark / Monsell, Sarah / Mock, Charles / Zhou, Xiao Hua / Thomas, Nicole / Robichaud, Elizabeth / Dean, Margaret / Hubbard, Janene / Jacka, Mary / Schwabe-Fry, Kristen / Wu, Joylee / Phelps, Creighton / Morris, John C / Anonymous920967. ·Department of Epidemiology, National Alzheimer's Coordinating Center, University of Washington, Seattle, WA. · Institute for Healthy Aging and Lifespan Studies and School of Urban and Regional Planning, Florida Atlantic University, Boca Raton, FL. · Department of Neurology, Mayo Clinic, Rochester, MN. · Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, Los Angeles. · Department of Neurosciences, University of California San Diego, La Jolla, CA. · Departments of Psychiatry and Neurology, and Cognitive Neurology and Alzheimer's Disease Center, Northwestern University Feinberg School of Medicine, Chicago, IL. · Department of Neurology, University of Kentucky, Lexington, KY. · Department of Medicine, University of Wisconsin School of Medicine and Public Health. · Department of Neurology, School of Medicine, University of Kansas, Kansas City, KS. · Department of Neurology, School of Medicine, Oregon Health & Science University, Portland, OR. · Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia. · Department of Psychiatry, University of Pittsburgh School of Medicine. · Department of Neurology, University of Pittsburgh School of Medicine. · Mental Illness Research, Education, and Clinical Center, VA Pittsburgh Healthcare System, Pittsburgh, PA. · Center for Biomedical Statistics, University of Washington, Seattle, WA. · National Institute on Aging (retired), Bethesda, MD. · Department of Neurology, Washington University School of Medicine, St. Louis, MO. ·Alzheimer Dis Assoc Disord · Pubmed #30376508.

ABSTRACT: INTRODUCTION: In 2015, the US Alzheimer's Disease Centers (ADC) implemented Version 3 of the Uniform Data Set (UDS). This paper describes the history of Version 3 development and the UDS data that are freely available to researchers. METHODS: UDS Version 3 was developed after years of coordination between the National Institute on Aging-appointed Clinical Task Force (CTF), clinicians from ∼30 ADCs, and the National Alzheimer's Coordinating Center (NACC). The CTF recognized the need for updates to align with the state of the science in dementia research, while being flexible to the diverse needs and diseases studied at the ADCs. Version 3 also developed a nonproprietary neuropsychological battery. RESULTS: This paper focuses on the substantial Version 3 changes to the UDS forms related to clinical diagnosis and characterization of clinical symptoms to match updated consensus-based diagnostic criteria. Between March 2015 and March 2018, 4820 participants were enrolled using UDS Version 3. Longitudinal data were available for 25,337 of the 37,568 total participants using all UDS versions. DISCUSSION: The results from utilization of the UDS highlight the possibility for numerous research institutions to successfully collaborate, produce, and use standardized data collection instruments for over a decade.

13 Review Nrf2 Pathway in Age-Related Neurological Disorders: Insights into MicroRNAs. 2018

Paladino, Simona / Conte, Andrea / Caggiano, Rocco / Pierantoni, Giovanna Maria / Faraonio, Raffaella. ·Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy. · CEINGE-Biotecnologie Avanzate s.c.a.r.l, Naples, Italy. · Lymphocyte Nuclear Biology, NIAMS, NIH, Bethesda, Maryland, USA. ·Cell Physiol Biochem · Pubmed #29969760.

ABSTRACT: A general hallmark of neurological diseases is the loss of redox homeostasis that triggers oxidative damages to biomolecules compromising neuronal function. Under physiological conditions the steady-state concentrations of reactive oxygen species (ROS) and reactive nitrogen species (RNS) are finely regulated for proper cellular functions. Reduced surveillance of endogenous antioxidant defenses and/or increased ROS/RNS production leads to oxidative stress with consequent alteration of physiological processes. Neuronal cells are particularly susceptible to ROS/RNS due to their biochemical composition. Overwhelming evidences indicate that nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-linked pathways are involved in protective mechanisms against oxidative stress by regulating antioxidant and phase II detoxifying genes. As such, Nrf2 deregulation has been linked to both aging and pathogenesis of many human chronic diseases, including neurodegenerative ones such as Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis. Nrf2 activity is tightly regulated by a fine balance between positive and negative modulators. A better understanding of the regulatory mechanisms underlying Nrf2 activity could help to develop novel therapeutic interventions to prevent, slow down or possibly reverse various pathological states. To this end, microRNAs (miRs) are attractive candidates because they are linked to intracellular redox status being regulated and, post-transcriptionally, regulating key components of ROS/RNS pathways, including Nrf2.

14 Review NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease. 2018

Jack, Clifford R / Bennett, David A / Blennow, Kaj / Carrillo, Maria C / Dunn, Billy / Haeberlein, Samantha Budd / Holtzman, David M / Jagust, William / Jessen, Frank / Karlawish, Jason / Liu, Enchi / Molinuevo, Jose Luis / Montine, Thomas / Phelps, Creighton / Rankin, Katherine P / Rowe, Christopher C / Scheltens, Philip / Siemers, Eric / Snyder, Heather M / Sperling, Reisa / Anonymous25330943. ·Department of Radiology, Mayo Clinic, Rochester, MN, USA. Electronic address: jack.clifford@mayo.edu. · Department of Neurological Sciences, Rush University, Chicago, IL, USA. · Department of Psychiatry and Neurochemistry, University of Gothenburg, Gothenburg, Sweden. · Medical & Scientific Relations, Alzheimer's Association, Chicago, IL, USA. · Office of Drug Evaluation, FDA, Silver Spring, MD, USA. · Biogen, Cambridge, MA, USA. · Department of Neurology, Washington University, St. Louis, MO, USA. · Department of Public Health and Neuroscience, University of California Berkeley, Berkeley, CA, USA. · Department of Psychiatry, University of Cologne, Medical Faculty, Cologne, Germany. · Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA. · Prothena Biosciences, Inc., San Francisco, CA, USA. · BarcelonaBeta Brain Research Center, Pasqual Maragall Foundation and Hospital Clinic-IDIBAPS, Barcelona, Spain. · Department of Pathology, Stanford University, Standford, CA, USA. · Formerly at National Institute on Aging, Bethesda, MD, USA. · Department of Neurology, University of California San Francisco, San Francisco, CA, USA. · Department of Molecular Imaging, Austin Health, University of Melbourne, Melbourne, Australia. · Department of Neurology, VU University Medical Center, Amsterdam, Netherlands. · Formerly at Eli Lilly and Company, Indianapolis, IN, USA. · Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA. ·Alzheimers Dement · Pubmed #29653606.

ABSTRACT: In 2011, the National Institute on Aging and Alzheimer's Association created separate diagnostic recommendations for the preclinical, mild cognitive impairment, and dementia stages of Alzheimer's disease. Scientific progress in the interim led to an initiative by the National Institute on Aging and Alzheimer's Association to update and unify the 2011 guidelines. This unifying update is labeled a "research framework" because its intended use is for observational and interventional research, not routine clinical care. In the National Institute on Aging and Alzheimer's Association Research Framework, Alzheimer's disease (AD) is defined by its underlying pathologic processes that can be documented by postmortem examination or in vivo by biomarkers. The diagnosis is not based on the clinical consequences of the disease (i.e., symptoms/signs) in this research framework, which shifts the definition of AD in living people from a syndromal to a biological construct. The research framework focuses on the diagnosis of AD with biomarkers in living persons. Biomarkers are grouped into those of β amyloid deposition, pathologic tau, and neurodegeneration [AT(N)]. This ATN classification system groups different biomarkers (imaging and biofluids) by the pathologic process each measures. The AT(N) system is flexible in that new biomarkers can be added to the three existing AT(N) groups, and new biomarker groups beyond AT(N) can be added when they become available. We focus on AD as a continuum, and cognitive staging may be accomplished using continuous measures. However, we also outline two different categorical cognitive schemes for staging the severity of cognitive impairment: a scheme using three traditional syndromal categories and a six-stage numeric scheme. It is important to stress that this framework seeks to create a common language with which investigators can generate and test hypotheses about the interactions among different pathologic processes (denoted by biomarkers) and cognitive symptoms. We appreciate the concern that this biomarker-based research framework has the potential to be misused. Therefore, we emphasize, first, it is premature and inappropriate to use this research framework in general medical practice. Second, this research framework should not be used to restrict alternative approaches to hypothesis testing that do not use biomarkers. There will be situations where biomarkers are not available or requiring them would be counterproductive to the specific research goals (discussed in more detail later in the document). Thus, biomarker-based research should not be considered a template for all research into age-related cognitive impairment and dementia; rather, it should be applied when it is fit for the purpose of the specific research goals of a study. Importantly, this framework should be examined in diverse populations. Although it is possible that β-amyloid plaques and neurofibrillary tau deposits are not causal in AD pathogenesis, it is these abnormal protein deposits that define AD as a unique neurodegenerative disease among different disorders that can lead to dementia. We envision that defining AD as a biological construct will enable a more accurate characterization and understanding of the sequence of events that lead to cognitive impairment that is associated with AD, as well as the multifactorial etiology of dementia. This approach also will enable a more precise approach to interventional trials where specific pathways can be targeted in the disease process and in the appropriate people.

15 Review Profiling donepezil template into multipotent hybrids with antioxidant properties. 2018

Mezeiova, Eva / Spilovska, Katarina / Nepovimova, Eugenie / Gorecki, Lukas / Soukup, Ondrej / Dolezal, Rafael / Malinak, David / Janockova, Jana / Jun, Daniel / Kuca, Kamil / Korabecny, Jan. ·a Biomedical Research Centre, University Hospital Hradec Kralove , Hradec Kralove , Czech Republic. · b National Institute of Mental Health , Klecany , Czech Republic. · d Department of Chemistry , University of Hradec Kralove , Hradec Kralove , Czech Republic. · c Department of Toxicology and Military Pharmacy, Faculty of Military Health Sciences , Hradec Kralove , Czech Republic. ·J Enzyme Inhib Med Chem · Pubmed #29529892.

ABSTRACT: Alzheimer's disease is debilitating neurodegenerative disorder in the elderly. Current therapy relies on administration of acetylcholinesterase inhibitors (AChEIs) -donepezil, rivastigmine, galantamine, and N-methyl-d-aspartate receptor antagonist memantine. However, their therapeutic effect is only short-term and stabilizes cognitive functions for up to 2 years. Given this drawback together with other pathological hallmarks of the disease taken into consideration, novel approaches have recently emerged to better cope with AD onset or its progression. One such strategy implies broadening the biological profile of AChEIs into so-called multi-target directed ligands (MTDLs). In this review article, we made comprehensive literature survey emphasising on donepezil template which was structurally converted into plethora of MTLDs preserving anti-cholinesterase effect and, at the same time, escalating the anti-oxidant potential, which was reported as a crucial role in the pathogenesis of the Alzheimer's disease.

16 Review Imaging Translocator Protein as a Biomarker of Neuroinflammation in Dementia. 2018

Kreisl, William C / Henter, Ioline D / Innis, Robert B. ·Taub Institute, Columbia University Medical Center, New York, NY, United States. Electronic address: wck2107@cumc.columbia.edu. · Molecular Imaging Branch, National Institute of Mental Health, Bethesda, MD, United States. ·Adv Pharmacol · Pubmed #29413519.

ABSTRACT: Neuroinflammation has long been considered a potential contributor to neurodegenerative disorders that result in dementia. Accumulation of abnormal protein aggregates in Alzheimer's disease, frontotemporal dementia, and dementia with Lewy bodies is associated with the activation of microglia and astrocytes into proinflammatory states, and chronic low-level activation of glial cells likely contributes to the pathological changes observed in these and other neurodegenerative diseases. The 18kDa translocator protein (TSPO) is a key biomarker for measuring inflammation in the brain via positron emission tomography (PET). Increased TSPO density has been observed in brain tissue from patients with neurodegenerative diseases and colocalizes to activated microglia and reactive astrocytes. Several radioligands have been developed to measure TSPO density in vivo with PET, and these have been used in clinical studies of different dementia syndromes. However, TSPO radioligands have limitations, including low specific-to-nonspecific signal and differential affinity to a polymorphism on the TSPO gene, which must be taken into consideration in designing and interpreting human PET studies. Nonetheless, most PET studies have shown that increased TSPO binding is associated with various dementias, suggesting that TSPO has potential as a biomarker to further explore the role of neuroinflammation in dementia pathogenesis and may prove useful in monitoring disease progression.

17 Review Newly Developed Drugs for Alzheimer's Disease in Relation to Energy Metabolism, Cholinergic and Monoaminergic Neurotransmission. 2018

Korábečný, Jan / Nepovimová, Eugenie / Cikánková, Tereza / Špilovská, Katarína / Vašková, Lucie / Mezeiová, Eva / Kuča, Kamil / Hroudová, Jana. ·Biomedical Research Centre, University Hospital Hradec Kralové, Sokolská 581, 500 05 Hradec Králové, Czech Republic; National Institute of Mental Health, Topolová 748, 250 67 Klecany, Czech Republic. · Biomedical Research Centre, University Hospital Hradec Kralové, Sokolská 581, 500 05 Hradec Králové, Czech Republic; Department of Psychiatry, First Faculty of Medicine, Charles University and General University Hospital in Prague, Ke Karlovu 11, 120 00 Prague 2, Czech Republic; Department of Chemistry, Faculty of Science, University of Hradec Králové, Rokitanského 62, 500 03 Hradec Králové, Czech Republic. · Department of Psychiatry, First Faculty of Medicine, Charles University and General University Hospital in Prague, Ke Karlovu 11, 120 00 Prague 2, Czech Republic. · National Institute of Mental Health, Topolová 748, 250 67 Klecany, Czech Republic; Department of Psychiatry, First Faculty of Medicine, Charles University and General University Hospital in Prague, Ke Karlovu 11, 120 00 Prague 2, Czech Republic; Department of Toxicology and Military Pharmacy, Faculty of Military Health Sciences, Třebešská 1575, 500 01 Hradec Králové, Czech Republic. · Department of Psychiatry, First Faculty of Medicine, Charles University and General University Hospital in Prague, Ke Karlovu 11, 120 00 Prague 2, Czech Republic; Department of Chemistry, Faculty of Science, University of Hradec Králové, Rokitanského 62, 500 03 Hradec Králové, Czech Republic. · Biomedical Research Centre, University Hospital Hradec Kralové, Sokolská 581, 500 05 Hradec Králové, Czech Republic; National Institute of Mental Health, Topolová 748, 250 67 Klecany, Czech Republic; Department of Psychiatry, First Faculty of Medicine, Charles University and General University Hospital in Prague, Ke Karlovu 11, 120 00 Prague 2, Czech Republic. · Biomedical Research Centre, University Hospital Hradec Kralové, Sokolská 581, 500 05 Hradec Králové, Czech Republic; Department of Chemistry, Faculty of Science, University of Hradec Králové, Rokitanského 62, 500 03 Hradec Králové, Czech Republic. · Department of Psychiatry, First Faculty of Medicine, Charles University and General University Hospital in Prague, Ke Karlovu 11, 120 00 Prague 2, Czech Republic; Institute of Pharmacology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Albertov 4, 128 00 Prague 2, Czech Republic. Electronic address: hroudova.jana@gmail.com. ·Neuroscience · Pubmed #28673719.

ABSTRACT: Current options for Alzheimer's disease (AD) treatment are based on administration of cholinesterase inhibitors (donepezil, rivastigmine, galantamine) and/or memantine, acting as an N-methyl-D-aspartate (NMDA). Therapeutic approaches vary and include novel cholinesterase inhibitors, modulators of NMDA receptors, monoamine oxidase (MAO) inhibitors, immunotherapeutics, modulators of mitochondrial permeability transition pores (mPTP), amyloid-beta binding alcohol dehydrogenase (ABAD) modulators, antioxidant agents, etc. The novel trends of AD therapy are focused on multiple targeted ligands, where mostly ChE inhibition is combined with additional biological properties, positively affecting neuronal energy metabolism as well as mitochondrial functions, and possessing antioxidant properties. The present review summarizes newly developed drugs targeting cholinesterase and MAO, as well as drugs affecting mitochondrial functions.

18 Review Alzheimer's Disease-Related Dementias Summit 2016: National research priorities. 2017

Corriveau, Roderick A / Koroshetz, Walter J / Gladman, Jordan T / Jeon, Sophia / Babcock, Debra / Bennett, David A / Carmichael, S Thomas / Dickinson, Susan L-J / Dickson, Dennis W / Emr, Marian / Fillit, Howard / Greenberg, Steven M / Hutton, Michael L / Knopman, David S / Manly, Jennifer J / Marder, Karen S / Moy, Claudia S / Phelps, Creighton H / Scott, Paul A / Seeley, William W / Sieber, Beth-Anne / Silverberg, Nina B / Sutherland, Margaret L / Taylor, Angela / Torborg, Christine L / Waddy, Salina P / Gubitz, Amelie K / Holtzman, David M. ·From the National Institute of Neurological Disorders and Stroke (R.A.C., W.J.K., J.T.G., S.J., D.B., M.E., C.S.M., P.A.S., B.-A.S., M.L.S., C.L.T., A.K.G.), Bethesda, MD · Rush Alzheimer's Disease Center (D.A.B.), Rush University Medical Center, Chicago, IL · Department of Neurology (S.T.C.), David Geffen School of Medicine, University of California, Los Angeles · The Association for Frontotemporal Degeneration (S.L.-J.D.), Radnor, PA · Department of Neuroscience (D.W.D.), Mayo Clinic, Jacksonville, FL · The Alzheimer's Drug Discovery Foundation (H.F.) · Icahn School of Medicine at Mount Sinai (H.F.), New York, NY · Department of Neurology (S.M.G.), Massachusetts General Hospital, Harvard Medical School, Boston · Eli Lilly and Company (M.L.H.), Lilly Research Centre, Erl Wood Manor, Windlesham, UK · Department of Neurology (D.S.K.), Mayo Clinic Rochester, MN · Taub Institute for Research on Alzheimer's Disease and the Aging Brain (J.J.M., K.S.M.) and College of Physicians and Surgeons (K.S.M.), Columbia University, New York, NY · National Institute on Aging (C.H.P., N.B.S.), Bethesda, MD · Memory and Aging Center, Department of Neurology (W.W.S.), and Department of Pathology (W.W.S.), University of California San Francisco · Lewy Body Dementia Association (A.T.), Lilburn, GA · National Institute of Diabetes and Digestive and Kidney Diseases (S.P.W.), Bethesda, MD · and Knight Alzheimer's Disease Research Center (D.M.H.), Hope Center for Neurological Disorders (D.M.H.), and Department of Neurology (D.M.H.), Washington University in St. Louis, MO. ·Neurology · Pubmed #29117955.

ABSTRACT: Goal 1 of the National Plan to Address Alzheimer's Disease is to prevent and effectively treat Alzheimer disease and Alzheimer disease-related dementias by 2025. To help inform the research agenda toward achieving this goal, the NIH hosts periodic summits that set and refine relevant research priorities for the subsequent 5 to 10 years. This proceedings article summarizes the 2016 Alzheimer's Disease-Related Dementias Summit, including discussion of scientific progress, challenges, and opportunities in major areas of dementia research, including mixed-etiology dementias, Lewy body dementia, frontotemporal degeneration, vascular contributions to cognitive impairment and dementia, dementia disparities, and dementia nomenclature.

19 Review Informatics Support for Basic Research in Biomedicine. 2017

Rindflesch, Thomas C / Blake, Catherine L / Fiszman, Marcelo / Kilicoglu, Halil / Rosemblat, Graciela / Schneider, Jodi / Zeiss, Caroline J. ·Lister Hill National Center for Biomedical Communications, National Library of Medicine, Bethesda, Maryland. School of Information Sciences, University of Illinois, Urbana-Champaign; Center for Informatics in Science and Scholarship. Lister Hill National Center for Biomedical Communications, National Library of Medicine, Bethesda, Maryland. Lister Hill National Center for Biomedical Communications, National Library of Medicine, Bethesda, Maryland. Lister Hill National Center for Biomedical Communications, National Library of Medicine, Bethesda, Maryland. School of Information Sciences, University of Illinois Urbana-Champaign, Champaign, Illinois. Yale University School of Medicine, New Haven, Connecticut. ·ILAR J · Pubmed #28838071.

ABSTRACT: Informatics methodologies exploit computer-assisted techniques to help biomedical researchers manage large amounts of information. In this paper, we focus on the biomedical research literature (MEDLINE). We first provide an overview of some text mining techniques that offer assistance in research by identifying biomedical entities (e.g., genes, substances, and diseases) and relations between them in text.We then discuss Semantic MEDLINE, an application that integrates PubMed document retrieval, concept and relation identification, and visualization, thus enabling a user to explore concepts and relations from within a set of retrieved citations. Semantic MEDLINE provides a roadmap through content and helps users discern patterns in large numbers of retrieved citations. We illustrate its use with an informatics method we call "discovery browsing," which provides a principled way of navigating through selected aspects of some biomedical research area. The method supports an iterative process that accommodates learning and hypothesis formation in which a user is provided with high level connections before delving into details.As a use case, we examine current developments in basic research on mechanisms of Alzheimer's disease. Out of the nearly 90 000 citations returned by the PubMed query "Alzheimer's disease," discovery browsing led us to 73 citations on sortilin and that disorder. We provide a synopsis of the basic research reported in 15 of these. There is wide-spread consensus among researchers working with a range of animal models and human cells that increased sortilin expression and decreased receptor expression are associated with amyloid beta and/or amyloid precursor protein.

20 Review Gene Linkage and Systems Biology. 2017

Cookson, Mark R. ·Laboratory of Neurogenetics, NIA, NIH. 35, Convent Drive, Bethesda, MD, 20892-3707, USA. cookson@mail.nih.gov. ·Adv Neurobiol · Pubmed #28674994.

ABSTRACT: In the past two decades it has become increasingly clear that the risk for many neurodegenerative disorders is at least partially genetic. Assignment of causality for a given gene depends on showing that a particular variant shows either segregation within a family or association with disease across a population. In terms of lifetime risk of disease, the former generally show strong effects compared to the latter. In rare, but interesting, circumstances there are genetic loci that contain different variants that encode either highly penetrant Mendelian disease but also that contribute to risk of sporadic disease. Here, we will discuss the current efforts to complete our understanding of the genetic architecture of neurodegenerative diseases of aging with a particular focus on Parkinson's disease. We will also briefly outline attempts to use systematic approaches to infer relationships between genes associated with the same diseases, which likely demonstrate that in each case there are a relatively small number of underlying biological pathways or processes that may explain pathogenesis.

21 Review Blood-brain barrier pericyte importance in malignant gliomas: what we can learn from stroke and Alzheimer's disease. 2017

Jackson, Sadhana / ElAli, Ayman / Virgintino, Daniela / Gilbert, Mark R. ·National Cancer Institute, Neuro-oncology Branch, Bethesda, Maryland; Research Center of CHU de Québec-Université Laval, Neuroscience Axis, Quebec, Canada; Department of Basic Medical Sciences, Neurosciences, and Sensory Organs, Human Anatomy and Histology Unit, University of Bari School of Medicine, Bari, Italy. ·Neuro Oncol · Pubmed #28541444.

ABSTRACT: The pericyte, a constitutive component of the central nervous system, is a poorly understood cell type that envelops the endothelial cell with the intended purpose of regulating vascular flow and endothelial cell permeability. Previous studies of pericyte function have been limited to a small number of disease processes such as ischemic stroke and Alzheimer's disease. Recently, publications have postulated a link between glioma stem cell differentiation and pericyte function. These studies suggest that there may be an important interaction of pericytes with tumor cells and other components of the tumor microenvironment in malignant primary glial neoplasms, most notably glioblastoma. This potential cellular interaction underscores the need to pursue more investigations of pericytes in malignant brain tumor biology. In this review, we summarize the functional roles of pericytes, particularly focusing on changes in pericyte biology during response to immune cells, inflammation, and hypoxic conditions. The information presented is based on the available data from studies of pericyte function in other central nervous system diseases but will serve as a foundation for research investigations to further understand the role of pericytes in malignant gliomas.

22 Review Exploring the nexus of Alzheimer's disease and related dementias with cancer and cancer therapies: A convening of the Alzheimer's Association & Alzheimer's Drug Discovery Foundation. 2017

Snyder, Heather M / Ahles, Tim / Calderwood, Stuart / Carrillo, Maria C / Chen, Honglei / Chang, Chung-Chou H / Craft, Suzanne / De Jager, Philip / Driver, Jane A / Fillit, Howard / Knopman, David / Lotze, Michael / Tierney, Mary C / Petanceska, Suzana / Saykin, Andrew / Seshadri, Sudha / Shineman, Diana / Ganguli, Mary. ·Division of Medical and Scientific Relations, Alzheimer's Association, Chicago, IL, USA. Electronic address: hsnyder@alz.org. · Department of Psychiatry and Behavioral Sciences, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Radiation Oncology, Harvard University Medical School, Boston, MA, USA. · Division of Medical and Scientific Relations, Alzheimer's Association, Chicago, IL, USA. · Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI, USA. · Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Biostatistics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA; Department of Biostatistics, University of Pittsburgh Medical School, Pittsburgh, PA, USA; Clinical and Translational Science, University of Pittsburgh Medical School, Pittsburgh, PA, USA. · Division of Gerontology and Geriatric Medicine, Department of Internal Medicine, Wake Forest University of Medicine, Winston-Salem, NC, USA. · Geriatric Research Education and Clinical Center, VA Boston HealthCare System, Boston, MA, USA. · Division of Aging, Brigham and Women's Hospital, Boston, MA, USA; Department of Medicine, Harvard University Medical School, Boston, MA, USA. · Scientific Affairs, Alzheimer's Drug Discovery Foundation, New York, NY, USA. · Department of Neurology, Mayo Clinic, Rochester, MN, USA. · Departments of Surgery, Immunology and Bioengineering, University of Pittsburgh Medical School, Pittsburgh, PA, USA. · Department of Family and Community Medicine, Sunnybrook Health Science Center, Toronto, Ontario, Canada. · Division of Neurosciences, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA. · Department of Radiology, Indiana University School of Medicine, Indianapolis, IN, USA. · Division of Neurology, Boston University Medical School, Boston, MA, USA. · Professor of Psychiatry, Neurology, and Epidemiology, University of Pittsburgh School of Medicine and Graduate School of Public Health, Pittsburgh, PA, USA. ·Alzheimers Dement · Pubmed #27998721.

ABSTRACT: Recent population studies suggest an intriguing inverse relationship between several types of cancer and neurodegenerative diseases, including Alzheimer's disease. Understanding the intersection of the underlying biology for these two distinct families of diseases with one another may offer novel approaches to identify new therapeutic approaches and possible opportunities to repurpose existing drug candidates. The Alzheimer's Association and the Alzheimer's Drug Discovery Foundation convened a one-day workshop to delve into this discussion. Workshop participants outlined research focus areas, potential collaborations, and partnerships for future action.

23 Review Multitarget Tacrine Hybrids with Neuroprotective Properties to Confront Alzheimer's Disease. 2017

Spilovska, Katarina / Korabecny, Jan / Nepovimova, Eugenie / Dolezal, Rafael / Mezeiova, Eva / Soukup, Ondrej / Kuca, Kamil. ·Department of Toxicology and Military Pharmacy, Faculty of Military Health Sciences, Trebesska 1575, 500 01 Hradec Kralove, Czech Republic. · National Institute of Mental Health, Topolova 748, 250 67 Klecany,. Czech Republic. · Biomedical Research Centre, University Hospital, Sokolska 581, 500 05 Hradec Kralove, Czech Republic. · National Institute of Mental Health, Topolova 748, 250 67 Klecany, Czech Republic. ·Curr Top Med Chem · Pubmed #27697055.

ABSTRACT: Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder. Several hallmarks such as β-amyloid (Aβ) aggregation underlying amyloid plaque formation, τ-hyperphosphorylation leading to production of neurofibrillary tangles, and decline in the number of cholinergic neurons appear to be fundamental in the pathophysiology of the disease. Other evidence points also to the involvement of oxidative stress, biometal dyshomeostasis, inflammation, and cell cycle regulatory failure. Taking into account such premises, many attractive targets for the development of anti-AD drugs have emerged. Specifically, the multifactorial nature of AD calls for multi-target-directed ligands (MTDLs) which can be beneficial by providing interactions with multiple targets. Tacrine (THA), the first clinically effective acetylcholinesterase inhibitor, was approved for the treatment of mild to moderate AD. Unfortunately, frequent adverse effects including peripheral cholinergic effects and hepatotoxicity limited its therapeutic potential. Based on the numerous biological systems involved in AD progression, this review covers THA-incorporated hybrids possessing a neuroprotective profile. In particular, it focuses on THA hybrids capable of scavenging reactive oxygen species (ROS), and derivatives which reduce the formation of Aβ-plaques either directly by confronting the Aβ1-42 selfaggregation process or indirectly by inhibiting the BACE-1 enzyme or AChE-induced Aβ1-40 aggregation. Particular interest is also addressed to THA hybrids with suppressed hepatotoxicity.

24 Review Nocardia asteroides-Induced movement abnormalities in mice: Relevance for Parkinson's disease? 2016

Loeffler, David A / LeWitt, Peter A / Camp, Dianne M. ·Department of Neurology, Beaumont Hospital-Royal Oak, Beaumont Health, Royal Oak, Michigan, USA. · Department of Neurology, Henry Ford West Bloomfield Hospital, West Bloomfield, Michigan, USA. · Department of Neurology, Wayne State University School of Medicine, Detroit, Michigan, USA. · National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health, Bethesda, Maryland, USA. ·Mov Disord · Pubmed #27411508.

ABSTRACT: -- No abstract --

25 Review Cytokine Therapies in Neurological Disease. 2016

Azodi, Shila / Jacobson, Steven. ·Viral Immunology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, 20892, USA. · Viral Immunology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, 20892, USA. jacobsons@ninds.nih.gov. ·Neurotherapeutics · Pubmed #27388288.

ABSTRACT: Cytokines are a heterogeneous group of glycoproteins that coordinate physiological functions. Cytokine deregulation is observed in many neurological diseases. This article reviews current research focused on human clinical trials of cytokine and anticytokine therapies in the treatment of several neurological disease including stroke, neuromuscular diseases, neuroinfectious diseases, demyelinating diseases, and neurobehavioral diseases. This research suggests that cytokine therapy applications may play an important role in offering new strategies for disease modulation and treatment. Further, this research provides insights into the causal link between cytokine deregulation and neurological diseases.

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