Deprecated: Function curl_close() is deprecated since 8.5, as it has no effect since PHP 8.0 in /home/u483256323/domains/poorvam.com/public_html/subdomains/pore/includes/api.php on line 184
Abstract
<title>Abstract</title> <p>Microglia occupy diverse inflammatory and lipid-processing states in Alzheimer's disease (AD), but whether broad metabolic transcriptional programs vary mainly by cell state or track regional neuropathological burden remains unclear. We analyzed the open Seattle Alzheimer's Disease Brain Cell Atlas (SEA-AD) multiregion single-nucleus RNA-sequencing immune dataset, comprising 240,651 immune nuclei from 84 postmortem donors across 10 brain regions. Analyses included 236,002 nuclei assigned to six Micro-PVM supertypes. Seven curated programs representing glycolysis, oxidative phosphorylation, fatty acid metabolism, cholesterol homeostasis, the tricarboxylic acid cycle, the pentose phosphate pathway, and lysosome were scored from log-normalized expression and aggregated by donor and region. Generalized estimating equations tested associations with local continuous pseudo-progression score while accounting for repeated regions and adjusting for donor, tissue-quality, technical, and regional covariates. Metabolic profiles differed descriptively among annotated supertypes. However, in 497 donor-region profiles with complete local pathology data, no program was associated with local pathology after multiple-testing correction (all adjusted p values >= 0.586). Global-pathology, middle temporal gyrus-only, severely affected-donor exclusion, and state-specific analyses did not alter the overall conclusion. Broad metabolic transcriptional programs were organized by annotated Micro-PVM state but did not show robust monotonic relationships with regional AD pathology. Transcript-based pathway scores should not be interpreted as direct measurements of metabolic flux.</p>