The Mount Sinai Alzheimer Disease Research Center (MSADRC) continues its historic success in research by using its unprecedented resources and expertise to seize opportunities for innovative approaches to understand, treat, and ultimately prevent the earliest signs of cognitive loss due to Alzheimer's disease (AD) and other causes of dementia. We have conducted critical basic translational and clinical studies to characterize cognitive loss and dementia in the elderly. We have used the National Alzheimer's Project Act (NAPA) as a road map to focus our established strengths. We continue our commitment to therapeutic development with innovative and powerful systems biology approaches to establish networks that can identify new targets and select trial ready candidates through pharmacological repurposing and by using the novel opportunity offered by our role in the international stem cell consortium, to develop neural progenitors, approaches to find unique models for therapeutic targets. We will develop a trial ready registry of non- demented elders who are informed and eager to participate in prevention studies. We will expand our characterization of racially and ethnically diverse elders currently underrepresented in research, and ensure the opportunity for them to participate in clinical research fully, including genetic analysis, biomarker studies, and clinical trials. We will continue to collect brains from our well-characterized clinical populations and focus our efforts on the pathology associated with the transition from normal aging and cognitive impairment. Contributing to National Alzheimer's Coordinating Center resources with clinical, neuropathological, and neuroimaging data will be continued as well as our commitment to provide the National Cell Repository for AD with samples for every eligible participant in our cohort. In keeping with the recommendations of NAPA and the 2013 AD-Related Dementias Research Workshop to include in the study of AD- related disorders a specific focus on the contribution of vascular risks, we will build on our expertise by proposing 3 projects that focus on the intersection of type 2 diabetes (T2D) one of the most common comorbidities of the at risk age group of AD. In Project 1, we will characterize cognitive loss and dementia in T2D individuals, examining markers of AD and insulin resistance including inflammation and cerebrovascular disease to identify the individual contribution and interactive roles of each pathogenetic factor. Minority participation will be a major feature of ths project to assure that our findings are applicable to the most applicable and understudied individuals. In Project 2, our well-characterized participant cohorts and animal models will be used with stem cell technology to identify the contribution of insulin resistance through cell types. In project 3, we examine the effects of T2D and AD on angiogenesis and angiogenic complexes. Together these efforts are aimed at identifying targets for intervention and prevention of AD. The resources of the cores and opportunities of the projects support the multidisciplinary studies of the widest community of researchers in cognitive loss and dementia.

Public Health Relevance

The Mount Sinai Alzheimer Disease Research Center (MSADRC) is committed to using innovative approaches and new technologies to understand, treat, and ultimately prevent the earliest signs of cognitive impairment due to Alzheimer's disease (AD) and other dementias. Also, the basic, translational, and clinical resources will be aligned to explore the controversial intersection between Type 2 diabetes and AD. These two conditions are common and understanding underlying the commonalities in their pathogenetic mechanisms may lead to improved treatments for one or both diseases. To date, the MSADRC has made seminal contributions to therapeutic development in AD research and the proposed work holds equally great promise for discoveries that will change the fate of those suffering from AD as well as those at risk.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Specialized Center (P50)
Project #
5P50AG005138-32
Application #
9054744
Study Section
Special Emphasis Panel (ZAG1)
Program Officer
Silverberg, Nina B
Project Start
1997-05-01
Project End
2020-03-31
Budget Start
2016-06-01
Budget End
2017-03-31
Support Year
32
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Icahn School of Medicine at Mount Sinai
Department
Psychiatry
Type
Schools of Medicine
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029
Bryois, Julien; Garrett, Melanie E; Song, Lingyun et al. (2018) Evaluation of chromatin accessibility in prefrontal cortex of individuals with schizophrenia. Nat Commun 9:3121
Miller, M L; Ren, Y; Szutorisz, H et al. (2018) Ventral striatal regulation of CREM mediates impulsive action and drug addiction vulnerability. Mol Psychiatry 23:1328-1335
Fazio, Leonardo; Pergola, Giulio; Papalino, Marco et al. (2018) Transcriptomic context of DRD1 is associated with prefrontal activity and behavior during working memory. Proc Natl Acad Sci U S A 115:5582-5587
Gusev, Alexander; Mancuso, Nicholas; Won, Hyejung et al. (2018) Transcriptome-wide association study of schizophrenia and chromatin activity yields mechanistic disease insights. Nat Genet 50:538-548
Burke, Shanna L; Hu, Tianyan; Fava, Nicole M et al. (2018) Sex differences in the development of mild cognitive impairment and probable Alzheimer's disease as predicted by hippocampal volume or white matter hyperintensities. J Women Aging :1-25
Khan, Atlas; Liu, Qian; Wang, Kai (2018) iMEGES: integrated mental-disorder GEnome score by deep neural network for prioritizing the susceptibility genes for mental disorders in personal genomes. BMC Bioinformatics 19:501
Wang, Jen-Chyong; Alinaghi, Somayeh; Tafakhori, Abbas et al. (2018) Genetic screening in two Iranian families with early-onset Alzheimer's disease identified a novel PSEN1 mutation. Neurobiol Aging 62:244.e15-244.e17
Crum, Jana; Wilson, Jeffrey; Sabbagh, Marwan (2018) Does taking statins affect the pathological burden in autopsy-confirmed Alzheimer's dementia? Alzheimers Res Ther 10:104
Wang, Qi; Guo, Lei; Thompson, Paul M et al. (2018) The Added Value of Diffusion-Weighted MRI-Derived Structural Connectome in Evaluating Mild Cognitive Impairment: A Multi-Cohort Validation1. J Alzheimers Dis 64:149-169
Burke, Shanna L; Cadet, Tamara; Maddux, Marlaina (2018) Chronic Health Illnesses as Predictors of Mild Cognitive Impairment Among African American Older Adults. J Natl Med Assoc 110:314-325

Showing the most recent 10 out of 555 publications