Albert Einstein College of Medicine receives $3.6 million NIH grant to investigate potential cause of Alzheimer's diseas

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).

Provided by Albert Einstein College of Medicine