Abstract
The microenvironment of the central nervous system is highly complex and plays a crucial role in maintaining the function of neurons, which influences Alzheimer's disease (AD) progression. The pH value of the brain is a critical aspect of the brain microenvironment in regulating various physiological processes. However, the specific mechanisms and role of this mechanism are not yet fully understood. To better understand the relationship between brain pH and AD, we analyzed the brain pH of the frontal lobe and AD pathology scores in postmortem brain samples from 368 donors from the National Human Brain Bank for Development and Function, 96 of whom were diagnosed with AD pathology. Analysis revealed a significant decrease in brain pH in AD patients, which was strongly correlated with β-amyloid plaques and phosphorylated tau proteins. Here, we elucidated the differential protein expression level of CD68-positive microglia between control and AD groups (t = 3.198, df = 20, P = 0.0045), and its protein expression level was correlated negatively with the brain pH value (F = 26.93, p = 0.0006). Our findings revealed that increased activation of CD68-positive microglia and disrupted lysosomal homeostasis in the pathological brain tissue of individuals with AD may lead to a decrease in brain pH.