Decreased Brain pH Correlated With Progression of Alzheimer Disease Neuropathology: A Systematic Review and Meta-Analyses of Postmortem Studies

Abstract Background Altered brain energy metabolism is implicated in Alzheimer disease (AD). Limited and conflicting studies on brain pH changes, indicative of metabolic alterations associated with neural activity, warrant a comprehensive investigation into their relevance in this neurodegenerative condition. Furthermore, the relationship between these pH changes and established AD neuropathological evaluations, such as Braak staging, remains unexplored. Methods We conducted quantitative meta-analyses on postmortem brain and cerebrospinal fluid pH in patients with AD and non-AD controls using publicly available demographic data. We collected raw pH data from studies in the NCBI GEO, PubMed, and Google Scholar databases. Results Our analysis of 20 datasets (723 patient samples and 524 control samples) using a random-effects model showed a significant decrease in brain and cerebrospinal fluid pH in patients compared with controls (Hedges’ g = −0.57, P