Alzheimer's disease (AD) research at The Friedman Brain Institute integrates basic, clinical and translational research to understand the molecular basis of the disease and improve treatment.
Alzheimer’s Disease & Related Dementias
AD is the most common cause of dementia (impairment of memory and thinking) 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. Over a period of years impairment becomes more widespread affecting cognition, problem solving, orientation and activities of daily living. 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 of the disease in which first beta-amyloid plaques and then neurofibrillary tangles accumulate, leading to neurodegeneration and ultimately to clinical symptoms. This presymptomatic phase of the disease can be detected using either neuroimaging or cerebrospinal fluid biomarkers.
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. Other studies by Mount Sinai faculty have demonstrated that TYRO protein tyrosine kinase binding protein (TYROBP) and triggering receptor expressed on myeloid cells 2 (TREM2) are part of an inflammatory protein network that influences risk for AD and is dysregulated in disease. We are also using state-of-the-art induced pluripotent stem cell methods to generated cellular models of AD and transgenic approaches to model disease in animals. Basic and translational research on AD and related disorders is carried out by investigators in the Center for Alzheimer’s Disease.
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. The mission of the center is to provide expertise in basic and clinical research for investigators both within and beyond the Mount Sinai community. Through many national and international collaborations the Investigators at Mount Sinai have access to clinical data sets, tissue and cell repositories and funding opportunities. 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) , composed of a multi-disciplinary team of neurologists, psychiatrists, neuropsychologists, neuroscientists and patient care managers. Using a fully integrated approach to brain and behavior, the CCH offers comprehensive diagnosis and treatment for a wide range of cognitive disorders. It is also supported through the Martha Stewart Center for Living, a state of the art outpatient facility in the department of geriatrics involved in in many research projects on the science and aging, including studying the neurobiology of aging, innovative educational initiatives, dementia, management of pain and delirium, Within this infrastructure of the ADRC 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.
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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- Alzheimer's Disease Research Center (ADRC)
- Human Embryonic Stem Cell
- ADND Club (Alzheimer's Disease and Neurodegeneration Club)
- Center for Cognitive Health
- Clinical Trials
- Department of Developmental and Regenerative Biology
- Geriatrics Patient Care Mount Sinai Hospital
- Department of Genetics and Genomic Sciences
- Department of Psychiatry
- Department of Neurology
- Department of Neuroscience
- Department of Neurosurgery