- Main
Beyond amyloid: Immune, cerebrovascular, and metabolic contributions to Alzheimer disease in people with Down syndrome
Published Web Location
https://doi.org/10.1016/j.neuron.2022.04.001Abstract
People with Down syndrome (DS) have increased risk of Alzheimer disease (AD), presumably conferred through genetic predispositions arising from trisomy 21. These predispositions necessarily include triplication of the amyloid precursor protein (APP), but also other Ch21 genes that confer risk directly or through interactions with genes on other chromosomes. We discuss evidence that multiple genes on chromosome 21 are associated with metabolic dysfunction in DS. The resulting dysregulated pathways involve the immune system, leading to chronic inflammation; the cerebrovascular system, leading to disruption of the blood brain barrier (BBB); and cellular energy metabolism, promoting increased oxidative stress. In combination, these disruptions may produce a precarious biological milieu that, in the presence of accumulating amyloid, drives the pathophysiological cascade of AD in people with DS. Critically, mechanistic drivers of this dysfunction may be targetable in future clinical trials of pharmaceutical and/or lifestyle interventions.
Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.
Main Content
Enter the password to open this PDF file:
-
-
-
-
-
-
-
-
-
-
-
-
-
-