RT Journal Article
SR Electronic
T1 Transcriptomic analysis of brain hypometabolism links the cholinergic and gingipain hypotheses of Alzheimer's disease pathogenesis
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2019.12.23.887364
DO 10.1101/2019.12.23.887364
A1 Sejal Patel
A1 Derek Howard
A1 Alana Man
A1 Deborah Schwartz
A1 Joelle Jee
A1 Daniel Felsky
A1 Zdenka Pausova
A1 Tomas Paus
A1 Leon French
YR 2019
UL http://biorxiv.org/content/early/2019/12/26/2019.12.23.887364.1.abstract
AB Alzheimer's disease (AD) starts decades before clinical symptoms appear. Low glucose utilization in regions of the cerebral cortex mark early AD and is informative for clinical diagnosis. To identify these specific regions, we conducted a meta-analysis of positron emission tomography studies that compared AD patients with healthy controls. Using the Allen Human Brain Atlas, we then identified genes with expression patterns associated with this hypometabolism map. Of the six brains in the Atlas, one demonstrated a strong spatial association with the hypometabolism pattern. Within this brain, genes encoding cytosolic ribosome proteins are highly expressed in the hypometabolic regions. Analyses of human and mouse data show that expression of these genes increases across AD-associated states of microglial activation, is high in acetylcholine-rich brain regions and neurons, and is up-regulated in inflamed gingival tissue. Taken together, our molecular characterization of cortical hypometabolism links the cholinergic and gingipain hypotheses of AD.