Neuropathological and transcriptomic characteristics of the aged brain

Area of Science:

• Neuroscience
• Genomics
• Aging Research

Background:

• Age-related neurodegenerative diseases pose a growing public health challenge.
• Current Alzheimer's disease (AD) treatments targeting amyloid beta have shown limited efficacy.
• Individual resilience to neuropathology varies significantly with age.

Purpose of the Study:

• To provide a comprehensive resource of neuropathological, molecular, and transcriptomic data from aged human brains.
• To investigate the relationship between AD pathology, cognitive function, and gene expression in aging.
• To identify factors influencing variability in cognitive aging.

Main Methods:

• Analysis of neuropathology, molecular data, and transcriptomics from 107 aged donors (median age 90) from the Adult Changes in Thought (ACT) study.
• Characterization of hippocampus and two cortical regions.
• Correlation analysis of gene expression with tau pathology and inflammation markers.

Main Results:

• Confirmed associations between AD pathology and dementia, with notable age-related variability.
• Identified co-expressed gene sets linked to pathological tau and inflammation.
• Demonstrated a relationship between dementia and RNA quality, suggesting its influence on transcriptomic studies.

Conclusions:

• Individual variability in resilience to neuropathology is a key factor in cognitive aging.
• Gene expression patterns correlate with specific pathologies and inflammation.
• Controlling for RNA quality is crucial for accurate dementia and aging research.