Tau and β-Amyloid Are Associated with Medial Temporal Lobe Structure, Function, and Memory Encoding in Normal Aging.

Area of Science:

• Neuroscience
• Gerontology
• Alzheimer's Disease Research

Background:

• Normal aging involves episodic memory decline and accumulation of beta-amyloid (Aβ) and tau proteins in the medial temporal lobe (MTL).
• The interplay between Aβ, tau, neural activity, and brain structure in aging-related memory impairment is not fully understood.
• Previous studies primarily focused on Aβ, leaving the combined impact of Aβ and tau on memory and brain changes unclear.

Purpose of the Study:

• To investigate the associations between in vivo measured Aβ and tau levels, neural activity during memory encoding, and MTL structure in cognitively normal older adults.
• To determine how pathological neural activity relates to memory performance and MTL atrophy.
• To elucidate the specific role of tau in mediating the relationship between protein aggregation and brain atrophy.

Main Methods:

• Utilized in vivo human Aβ and tau imaging (PET).
• Employed functional magnetic resonance imaging (fMRI) to assess neural activity during memory encoding.
• Conducted mediation analysis to explore the role of tau in brain atrophy.

Main Results:

• Increased Aβ and tau were both linked to aberrant fMRI activity in the MTL during memory encoding.
• This aberrant neural activity correlated with poorer memory performance and MTL atrophy.
• Mediation analysis indicated that MTL tau explained the association between protein aggregation and regional atrophy.

Conclusions:

• Findings suggest that Aβ and tau aggregation contribute to age-related memory decline through aberrant neural activity and structural changes in the MTL.
• This study expands the understanding of cognitive aging by incorporating Alzheimer's disease-related pathology as a mechanism for memory impairment.
• The results highlight distinct but related roles for Aβ and tau in memory encoding deficits and brain atrophy in normal aging.