Researchers map protein-gene interactions involved in Alzheimer's disease

Disconcerting challenges in the diagnosis and treatment of Alzheimer's disease include the fact that patients with asymptomatic and symptomatic versions of degenerative disease may share similar neuropathological burden, but have significantly different rates of cognitive decline. .

In a new study published on July 23, 2019 in Cell reports, a team led by researchers at the University of California San Diego School of Medicine used the transcriptome – the sum of all the messenger RNA molecules (mRNAs) expressed from genes – for compare 414 participants in a diagnosed and neuropathologically confirmed MA with a matched age, non-demented control group derived from a community-based neuropathological study.

Their results suggest that the integration of protein interactions with gene perturbations can generate a complete framework for characterizing AM-related molecular network alterations.

While familial AD has a significant genetic factor, the causes of sporadic AD (the most common form) are multiple and not completely known. The main risk factors include age, bad and family history, but also various biological, psychological and social factors.

Much research has focused on two key elements of the pathology of AD: the accumulation of amyloid protein plaques and the abnormal tangles of neurofibrillary tau proteins in the brain, likely to cause dysfunction and death of neurons. But scientists are increasingly recognizing the relevance and importance of other factors, such as inflammation, blood flow problems, and brain atrophy, all of which "correlate with the clinical symptoms of cognitive decline." and have led to a change in diagnostic criteria over the last decade. " authors.

The new study combined badyzes of gene disruption and protein interactions, said lead author Robert Rissman, PhD, professor of neuroscience at the University of San Diego School of Medicine, director of the Biomarker for the Study. Co-operative on Alzheimer's Disease (ADCS) and Director of Neuropathology. / Brain Bank and Biomarker Core for the San Diego-based Alzheimer's Disease Research Center Shiley-Marcos, which ultimately identified clusters of functionally distinct genes, revealing profound changes in AD expression levels. These groups broadly corresponded to synaptic transmission, metabolism, cell cycle, cell survival, and immune response – all critical aspects involved in the pathology of AD.

"One of the big problems of research on Alzheimer's disease is identifying patients at risk at the right time," Rissman said. "Understanding which gene networks are likely to change in specific patient groups can help streamline clinical trial recruitment efforts and reduce the costs and delays of trial recruitment. Pre-symptomatic disease, we need to deepen our understanding of the mechanisms that underlie the entire spectrum of the disease. "

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Co-authors include: Saranya Canchi, UC San Diego and San Diego Veterans Health Care System; Balaji Raao, Deborah Masliah, Sara Brin Rosenthal, Roman Sasik and Kathleen M. Fisch, all at UC San Diego; Philip L. De Jager, Medical Center of Columbia University; and David A. Bennett, Rush University Medical Center.