This is a renewal of a program previously entitled """"""""Cholinergic Treatment of Memory Deficits in the Aged"""""""". That program helped to develop the rationale, methods, and preliminary data for many of the large multi-site clinical trials, of potential treatments for Alzheimer's Disease (AD) which are now being supported by NIH and the pharmaceutical industry. The current proposal is designed to fill a major gap in our understanding of AD resulting from the fact that the great majority of clinical and biologic studies of AD involve patients with established and often advanced disease. Further advances in the diagnosis, treatment and prevention of AD will benefit greatly from a better understanding of the earliest biological and clinical changes in AD. The current proposal includes 5 scientific projects investigating persons at high risk for AD and comparing them with demographically matched groups of normal controls and AD patients. The groups to be studied longitudinally are: cognitively normal elderly, AD, AD, and elderly first degrees relatives of AD probands. A high proportion of persons in all groups except the first degree relatives will coke to autopsy during the 5 years of the proposed program. Project 1 will involve all groups and will test hypotheses about the neuropsychological changes in early AD will be tested using autopsy material in projects 3 and 5, respectively. Project 2 will test hypotheses about demographic factors, particularly age of onset, that may be associated with a greater genetic contribution to the development of AD. Project 4 will determine whether acute phase reactants, which are elevated in serum of some AD patients and some first degrees relatives are early indicators of AD and whether they are specific for amyloidogenic conditions. The ultimate aim of the program is to improve the diagnosis and treatment of AD through a better understanding of it's earliest manifestations.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZAG1 (J1))
Program Officer
Buckholtz, Neil
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Mount Sinai School of Medicine
Schools of Medicine
New York
United States
Zip Code
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
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
Girdhar, Kiran; Hoffman, Gabriel E; Jiang, Yan et al. (2018) Cell-specific histone modification maps in the human frontal lobe link schizophrenia risk to the neuronal epigenome. Nat Neurosci 21:1126-1136
Hauberg, Mads E; Fullard, John F; Zhu, Lingxue et al. (2018) Differential activity of transcribed enhancers in the prefrontal cortex of 537 cases with schizophrenia and controls. Mol Psychiatry :
Agrawal, A; Chou, Y-L; Carey, C E et al. (2018) Genome-wide association study identifies a novel locus for cannabis dependence. Mol Psychiatry 23:1293-1302
Dobbyn, Amanda; Huckins, Laura M; Boocock, James et al. (2018) Landscape of Conditional eQTL in Dorsolateral Prefrontal Cortex and Co-localization with Schizophrenia GWAS. Am J Hum Genet 102:1169-1184
Gandal, Michael J; Haney, Jillian R; Parikshak, Neelroop N et al. (2018) Shared molecular neuropathology across major psychiatric disorders parallels polygenic overlap. Science 359:693-697
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
Giambartolomei, Claudia; Zhenli Liu, Jimmy; Zhang, Wen et al. (2018) A Bayesian framework for multiple trait colocalization from summary association statistics. Bioinformatics 34:2538-2545

Showing the most recent 10 out of 306 publications