April 21, 1016–(BRONX, NY)–Alzheimer's disease is the most common cause of dementia in older people. It occurs when amyloid precursor protein (APP) undergoes two sequential enzymatic cleavages, forming smaller clumps called amyloid-beta peptides (ABP) that accumulate between neurons in the brain.
Luciano D'Adamio, M.D., Ph.D., professor of microbiology & immunolog at Albert Einstein College of Medicine, has received a five-year, $3.6-million grant from the National Institutes of Health to continue his research into how APP is processed in the brain.
Genetic evidence suggests that the way APP is processed contributes to Alzheimer's disease. The protein is first cleaved by the enzyme beta-secretase 1 (BACE1). Some people–those possessing a variant of APP for which processing by BACE1 is reduced–are protected from developing Alzheimer's disease and from experiencing normal age-dependent cognitive decline. And mutations in genes that regulate APP processing are known to cause familial dementias. Yet little is known about the physiological relevance of APP processing or of APP itself.
Although best known for its involvement in Alzheimer's, APP also plays a key role in synaptic transmission, i.e., conveying neural impulses across synapses. The NIH grant will allow Dr. D'Adamio to analyze the role of APP (and of APLP2, a member of the APP protein family) in synaptic transmission and to investigate the molecular mechanisms that underlie it. He and his colleagues will also study how the processing of APP and APLP2 regulates synaptic transmission.
A better understanding of APP's synaptic function may shed light on the pathogenesis of Alzheimer's and reveal targets for drugs aimed at treating this devastating disease.
The grant is titled Mechanisms of APP and APLP2 Function at Synapses (R01AG052286).
About Albert Einstein College of Medicine
Albert Einstein College of Medicine is one of the nation's premier centers for research, medical education and clinical investigation. During the 2015-2016 academic year, Einstein is home to 731 M.D. students, 193 Ph.D. students, 106 students in the combined M.D./Ph.D. program, and 278 postdoctoral research fellows. The College of Medicine has more than 1,900 full-time faculty members located on the main campus and at its clinical affiliates. In 2015, Einstein received $148 million in awards from the National Institutes of Health (NIH). This includes the funding of major research centers at Einstein in aging, intellectual development disorders, diabetes, cancer, clinical and translational research, liver disease, and AIDS. Other areas where the College of Medicine is concentrating its efforts include developmental brain research, neuroscience, cardiac disease, and initiatives to reduce and eliminate ethnic and racial health disparities. Its partnership with Montefiore Medical Center, the University Hospital and academic medical center for Einstein, advances clinical and translational research to accelerate the pace at which new discoveries become the treatments and therapies that benefit patients. Through its extensive affiliation network involving Montefiore, Jacobi Medical Center–Einstein's founding hospital, and three other hospital systems in the Bronx, Brooklyn and on Long Island, Einstein runs one of the largest residency and fellowship training programs in the medical and dental professions in the United States. For more information, please visit www.einstein.yu.edu, read our blog, follow us on Twitter, like us on Facebook, and view us on YouTube.