53. DECREASED BRAIN PH CORRELATED WITH PROGRESSION OF ALZHEIMER’S DISEASE NEUROPATHOLOGY: A SYSTEMATIC REVIEW AND META-ANALYSES OF POSTMORTEM STUDIES

Abstract Background Altered brain energy metabolism is implicated in Alzheimer’s 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. Aims & Objectives The aim of this study is to gain comprehensive insights into the relevance of brain pH changes in AD. Method 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 to controls (Hedges’ g = -0.57, p < 0.0001). This decrease remained significant after considering postmortem interval, age at death, and sex. Notably, pH levels were negatively correlated with Braak stage, indicated by the random-effects model of correlation coefficients from 15 datasets (292 patient samples and 159 control samples) (adjusted r = -0.26, p < 0.0001). Furthermore, brain pH enhanced the discriminative power of the APOEε4 allele, the most prevalent risk gene for AD, in distinguishing patients from controls in a meta-analysis of four combined datasets (95 patient samples and 87 control samples). Discussion & Conclusions The significant decrease in brain pH in AD underlines its potential role in disease progression and diagnosis. This decrease, potentially reflecting neural hyperexcitation, could enhance our understanding of neurodegenerative pathology and aid in developing diagnostic strategies.