Donor specific transcriptomic analysis of Alzheimer's disease associated 8 hypometabolism highlights a unique donor, ribosomal proteins and microglia 9 2. Abbreviated Title (50 character maximum) RNA patterns of Alzheimer's disease hypometabolism 3. List all Author Names and Affiliations in order as they would appear in the published article

Alzheimer's disease (AD) starts decades before clinical symptoms appear. Low glucose utilization in regions of the cerebral cortex marks early AD and is clinically useful. 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 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. These proteins have a high proportion of arginine and lysine residues, which are cleaved by gingipains. Expression of these genes increases across AD-associated microglial activation, is high in acetylcholine-rich 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.

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