Fluorodeoxyglucose metabolism associated with tau-amyloid interaction predicts memory decline

Area of Science:

• Neuroscience
• Gerontology
• Biomedical Imaging

Background:

• Alzheimer's disease (AD) is characterized by amyloid and tau pathology.
• Understanding how these pathologies affect brain metabolism and cognition in preclinical stages is crucial.

Purpose of the Study:

• To evaluate the impact of amyloid and regional tauopathy on cerebral glucose metabolism and memory decline in normal older adults and those with preclinical AD.

Main Methods:

• Positron emission tomography (PET) scans were used to measure amyloid (C11 Pittsburgh compound B), tau (F18 flortaucipir), and glucose metabolism (F18 fluorodeoxyglucose).
• The study included 90 clinically normal elderly participants from the Harvard Aging Brain Study.

Main Results:

• High amyloid and neocortical tau were linked to decreased posterior cingulate metabolism and predicted memory decline.
• Age-related entorhinal tauopathy correlated with frontal hypometabolism, independent of amyloid, and did not predict memory decline.
• Neocortical tauopathy showed a positive association with metabolism in individuals with subthreshold amyloid, suggesting a biphasic effect.

Conclusions:

• A synergistic effect between amyloid and tau deposits was identified, linking them to AD-like hypometabolism and memory decline in normal elderly individuals.
• The observed effects were specific to neocortical tau, whereas age-related entorhinal tauopathy did not associate with memory loss.
• This research provides novel insights into the early metabolic and cognitive consequences of AD pathology in aging brains.