Subthreshold Amyloid Predicts Tau Deposition in Aging.

Area of Science:

• Neuroscience
• Gerontology
• Biomarker Research

Background:

• Current Alzheimer's disease (AD) detection relies on positive/negative amyloid-beta (Aβ) biomarker classification.
• Aβ accumulation begins years before biomarker abnormality, necessitating earlier detection methods.
• Understanding preclinical AD pathology is crucial for timely intervention.

Purpose of the Study:

• To investigate the earliest changes in AD pathology and their impact on memory in cognitively normal older adults.
• To explore the relationship between Aβ accumulation, tau deposition, and cognitive function.
• To identify potential targets for early intervention in preclinical AD.

Main Methods:

• Longitudinal [11C]Pittsburgh Compound B PET scanning and neuropsychological assessments in 71 cognitively normal older adults.
• [18F]AV-1451 PET scanning to measure tau deposition in a subset (N=37).
• Analysis of baseline Aβ levels, Aβ accumulation rates, and their correlation with tau pathology and memory decline.

Main Results:

• An inverted-U relationship was observed between baseline Aβ levels and Aβ slope, indicating slowing Aβ accumulation even in normal adults.
• In amyloid-negative participants, Aβ accumulation rate and baseline levels predicted early cortical tau deposition.
• Amyloid measures only correlated with memory decline when baseline Aβ levels were elevated, suggesting pathology precedes cognitive impact.

Conclusions:

• Amyloid measures are sensitive predictors of early tau deposition in preclinical AD.
• Aβ accumulation may slow in preclinical AD, suggesting it's a later stage of progression.
• Early intervention with amyloid-lowering therapies is crucial, even in individuals testing amyloid-negative, before significant cognitive decline.