Alzheimer's disease (AD) research at The Friedman Brain Institute integrates basic, clinical and translational research to better understand the molecular basis of the disease and improve treatment. Inter-disciplinary research programs span genetics and genomics, preclinical cellular and animal models, patient oriented research and clinical trials. Using state-of-the-art approaches, we continue to make breakthroughs in multiple aspects of dementia research. This diverse team publishes, more than 50 articles a year in prestigious peer-reviewed journals. Three interrelated centers focus on different aspects of Alzheimer’s disease including basic, translational and patient oriented research and clinical care: Center for Alzheimer’s Disease; the Alzheimer’s disease Research Center and the Center for Cognitive Health.
Alzheimer’s Disease & Related Dementias
There are more than sixty causes of dementia: impairment of memory and thinking. AD is the most common cause and is characterized clinically by gradual onset and progression of disease, usually in later life (>60yrs). Impairment of memory, particularly for recent events, is most often the initial symptom of disease. Death usually occurs within 5-20yrs. The AD brain is characterized by the abundant presence of beta-amyloid plaques and neurofibrillary tangles and substantial neuronal cell loss, particularly in the neocortex. It has recently been demonstrated that AD also involves a substantial (10-20yrs) presymptomatic phase in which first beta-amyloid plaques and then neurofibrillary tangles accumulate, leading to neurodegeneration and ultimately to clinical symptoms.
Investigators involved: Dongming Cai, John Crary, Dara L. Dickstein, Michelle Ehrlich, Samuel E. Gandy, Alison Goate, Ke Hao, Patrick R. Hof, Giulio M. Pasinetti, Nikolaos K. Robakis, Eric Schadt, Anne Schaefer, Bin Zhang
Frontotemporal dementia (FTD) is characterized clinically by early and prominent changes in personality and behavior. Some forms are also associated with profound aphasia. This form of dementia usually has an onset between 55-65yrs. Like AD, FTD is associated with protein deposits in the diseased brain. The most common form of FTD is associated with deposits of the RNA binding protein, TDP43. A second form of FTD is characterized by the presence of neuronal or glial tangles composed of tau protein (tauopathy). Genetic studies have demonstrated that FTD and amyotrophic lateral sclerosis (ALS) are etiologically related to one another. Mutations in several genes can lead to either FTD or ALS in family members.
Areas of Research
Genetics & Genomics of Alzheimer’s disease
AD is a complex genetic disorder. A small percentage of AD cases are inherited as an autosomal dominant trait (50% of the offspring of affected individuals develop disease). Among these cases three genes have been identified that can carry causative mutations: ß-amyloid protein precursor (APP), presenilin 1 (PSEN1) and presenilin 2 (PSEN2). Mutations in these genes are generally associated with an early age at onset (< 60yrs). Most cases of AD do not show such striking familial clustering and have an age at onset, which is usually >60yrs. Among this group the strongest genetic risk factor is the apolipoprotein E 4 allele. Presence of a single E4 allele increases risk by approximately 3 fold while 2 copies increases risk by as much as 10 fold. Genome-wide association studies have identified more than twenty loci and next generation sequencing studies have identified rare variants in other genes that influence risk for late onset AD (LOAD). These studies have implicated lipid metabolism, innate immunity and endocytic trafficking in risk for LOAD.
Understanding the molecular basis of Alzheimer’s disease
Mutations in APP and PSEN influence the cleavage of APP by beta and gamma secretases leading to higher levels of total Aß or Aß42, resulting in earlier amyloid aggregation and deposition. In contrast APOE influences clearance of Aß, with the risk allele for AD, APOE4, being less efficient at clearing Aß. For most other genes and proteins linked to AD risk, the underlying mechanisms remain unclear and are the focus of our research. Center investigators use a diverse range of approaches to understand disease mechanism including neuroimaging, genomics, cell-based studies including use of induced pluripotent stem cells and transgenic approaches.
Investigators involved: Dongming Cai, Dara L. Dickstein, Michelle Ehrlich, Samuel E. Gandy, Alison Goate, Ke Hao, Patrick R. Hof, Giulio M. Pasinetti, Nikolaos K. Robakis, Eric Schadt, Anne Schaefer, Bin Zhang
Advanced Clinical Care and Research
State of the art clinical care and research is supported by the Mount Sinai Alzheimer's Disease Research Center (ADRC), a nationally renowned center funded by the National Institute on Aging. Through the clinical resources of the ADRC comprehensive neuropsychological, genetic, biomarker and diagnostic characterization is conducted on a clinical cohort. This work is supported through a close collaboration with the Mount Sinai Center for Cognitive Health (CCH) and the Martha Stewart Center for Living. Within this infrastructure we design and conduct cutting edge clinical trials and studies to treat or prevent cognitive loss within a wide range of conditions including Alzheimer Disease, Mild Cognitive impairment, diabetes and traumatic brain injury. The core cohort is available for research studies and the core faculty can provide expertise in developing evaluations for other settings and studies. We also maintain extensive historical databases of these resources, which are available for researchers. Finally, we offer post mortem neuropathological analysis on brain tissue specimens from persons with Alzheimer’s disease and comparison groups. An extensive bank of this well characterized material is available to qualified researchers.
Investigators involved: Dongming Cai, Dara L. Dickstein, Michelle Ehrlich, Samuel E. Gandy, Alison Goate, Ke Hao, Patrick R. Hof, Giulio M. Pasinetti, Nikolaos K. Robakis, Mary Sano, Eric Schadt, Bin Zhang
Alzheimer's Disease Research Center
One Gustave L. Levy Place
New York, NY 10029
Phone: 718-584-9000 ext. 5199
James J. Peters VA Medical Center
130 West Kingsbridge Road
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