Biomarkers

Area of Science:

• Neuroimaging
• Neurodegeneration
• Alzheimer's Disease Research

Background:

• Hippocampal gray matter microstructure assessed via diffusion-weighted imaging (DWI) is a sensitive marker for neurodegeneration in Alzheimer's disease (AD).
• Microstructural changes in the hippocampus may precede volumetric loss, providing insights into early AD pathogenesis.
• Amyloid-beta (Aβ) and tau pathologies are key hallmarks of AD, influencing neurodegeneration and cognitive decline.

Purpose of the Study:

• To investigate the relationship between hippocampal microstructure (DWI), tau pathology (PET), and episodic memory.
• To examine the moderating role of amyloid-beta (Aβ) status on these associations.
• To determine if tau PET burden mediates the link between hippocampal microstructure and memory performance in individuals with varying Aβ status.

Main Methods:

• The study included 192 participants without dementia (14 with mild cognitive impairment [MCI]), with Aβ status determined by PET imaging.
• Multiple linear regression analyses were used to test for interactions between Aβ status, hippocampal mean diffusivity (MD), and tau PET burden.
• Episodic memory performance was assessed using a composite score.

Main Results:

• Increased hippocampal MD was associated with worse memory and greater tau PET burden, but only in amyloid-positive individuals.
• Amyloid-beta status significantly moderated the associations between hippocampal MD, tau PET, and memory.
• Tau PET burden fully mediated the relationship between elevated hippocampal MD and poorer memory performance in amyloid-positive participants, independent of hippocampal volume.

Conclusions:

• Hippocampal microstructure is sensitive to AD-related pathological burden and neurodegeneration, particularly in the early symptomatic stages.
• These findings highlight the interplay between Aβ status, tau pathology, hippocampal microstructure, and cognitive decline in early AD.
• DWI assessment of hippocampal microstructure may serve as a valuable biomarker for early AD detection and progression monitoring.