Tau pathology mediates age effects on medial temporal lobe structure

Area of Science:

• Neuroscience
• Gerontology
• Neuropathology

Background:

• Medial temporal lobe (MTL) atrophy, particularly in the hippocampus, is common in normal aging.
• The specific factors contributing to age-related MTL structural changes remain unclear.

Purpose of the Study:

• To investigate cross-sectional and longitudinal MTL atrophy patterns in cognitively normal older adults.
• To determine if white matter hyperintensities (WMHs) and cerebrospinal fluid (CSF) phospho-tau (p-tau) levels explain age-related MTL changes.

Main Methods:

• Analysis of cross-sectional (n=191) and longitudinal (n=164) data from the ADNI-GO/2 study.
• Assessment of MTL structural measures, WMHs, and CSF p-tau levels in participants with no to low cerebral β-amyloid.
• Mediation analyses to evaluate the role of CSF p-tau in age-related atrophy.

Main Results:

• Age was significantly associated with hippocampal volumes and Brodmann Area (BA) 35 thickness (cross-sectional).
• Age correlated with anterior/posterior hippocampus, entorhinal cortex, and BA35 (longitudinal).
• CSF p-tau levels were significantly associated with hippocampal volumes and atrophy rates, partially mediating age effects. WMHs showed no significant associations.

Conclusions:

• Tau pathology, potentially Primary Age-Related Tauopathy, plays a role in age-related MTL structural changes.
• CSF p-tau levels partially mediate age-related hippocampal atrophy.
• Findings suggest potential for tau-targeted interventions in mitigating age-associated neurodegeneration and memory decline.