From understanding to action: Exploring molecular connections of Down syndrome to Alzheimer's disease for targeted therapeutic approach

Author:

Sukreet Sonal1ORCID,Rafii Michael S.2ORCID,Rissman Robert A.13ORCID

Affiliation:

1. Department of Neurosciences University of California‐San Diego La Jolla California USA

2. Department of Neurology, Alzheimer's Therapeutic Research Institute Keck School of Medicine of the University of Southern California San Diego California USA

3. Department Physiology and Neuroscience, Alzheimer’s Therapeutic Research Institute Keck School of Medicine of the University of Southern California San Diego California USA

Abstract

AbstractDown syndrome (DS) is caused by a third copy of chromosome 21. Alzheimer's disease (AD) is a neurodegenerative condition characterized by the deposition of amyloid‐beta (Aβ) plaques and neurofibrillary tangles in the brain. Both disorders have elevated Aβ, tau, dysregulated immune response, and inflammation. In people with DS, Hsa21 genes like APP and DYRK1A are overexpressed, causing an accumulation of amyloid and neurofibrillary tangles, and potentially contributing to an increased risk of AD. As a result, people with DS are a key demographic for research into AD therapeutics and prevention. The molecular links between DS and AD shed insights into the underlying causes of both diseases and highlight potential therapeutic targets. Also, using biomarkers for early diagnosis and treatment monitoring is an active area of research, and genetic screening for high‐risk individuals may enable earlier intervention. Finally, the fundamental mechanistic parallels between DS and AD emphasize the necessity for continued research into effective treatments and prevention measures for DS patients at risk for AD. Genetic screening with customized therapy approaches may help the DS population in current clinical studies and future biomarkers.

Funder

National Institutes of Health

Publisher

Wiley

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