Brain gray matter volume mediated the relationship between plasma p‐tau and cognition of early Alzheimer’s disease

Abstract

AbstractBackgroundCognitive deterioration and atrophy of the brain gray matter volume (GMV) are the main symptoms of Alzheimer’s disease (AD). Accumulated pieces of evidence have shown that plasma concentrations of phosphorylated‐tau (p‐tau) performed better in early diagnosing, differentiating, and monitoring the progression of AD. However, the relationship between plasma p‐tau concentrations, the GMV of brain regions, and cognitive function remains poorly understood. Previous studies indicate that brain GMV may mediate the relationship between biomarkers and cognitive function, and in this study, we aimed to investigate whether GMV plays a mediating role in the association between plasma p‐tau concentrations and cognition.Method99 participants in total, including 47 patients with a diagnosis of early AD and 52 cognitively unimpaired (CU) individuals, were enrolled in this study. All participants completed laboratory tests, magnetic resonance imaging scans, and neuropsychological assessments. Plasma p‐tau217 and p‐tau181 concentrations were measured using an enzyme‐linked immunosorbent assay kit. Voxel‐based morphometry was performed to assess brain GMV. Partial correlations and mediation analyses were performed in the AD group.ResultConcentrations of both plasma p‐tau217 and p‐tau181 were significantly higher in the AD group than in the CU group. Patients with AD had significant brain GMV atrophy in the right hippocampus, bilateral middle temporal gyrus, and right inferior temporal gyrus. In the AD group, there were significant correlations between plasma p‐tau217 concentrations, GMV, and Mini‐Mental State Examination (MMSE) scores. Brain GMV of the right hippocampus mediated the association between plasma p‐tau217 concentrations and MMSE scores. We did not find a significant correlation between plasma p‐tau181 concentrations and MMSE scores.ConclusionThe findings indicate that p‐tau217 was a promising biomarker for central processes affecting brain GMV and cognitive function. It may provide potential targets for future intervention and treatment of tau‐targeting therapies at the early stage of AD.