Biomarkers

Area of Science:

• Neuroscience
• Neurology
• Biomarker Research

Background:

• Alzheimer's disease (AD) is characterized by progressive synaptic loss and cognitive decline.
• The interplay between tau pathology, neuroinflammation, and synaptic dysfunction in AD progression remains incompletely understood.

Purpose of the Study:

• To investigate the longitudinal associations between synaptic density changes, cognitive decline, and markers of tau pathology and neuroinflammation in Alzheimer's disease.
• To explore the predictive value of baseline tau pathology and plasma biomarkers for synaptic loss and cognitive decline.

Main Methods:

• Longitudinal study involving cognitively impaired (CI) individuals and healthy controls (HC).
• Utilized positron emission tomography (PET) for amyloid, tau, and synaptic density imaging ([18F]Florbetapir, [18F]MK6240, [18F]SynVesT-1).
• Assessed plasma biomarkers (p-tau 181, NfL, GFAP) and cognitive function (MMSE) over a one-year follow-up period. Employed statistical analyses including t-tests, correlation, general linear models, and mediation analyses.

Main Results:

• Cognitively impaired individuals exhibited greater longitudinal synaptic loss in the medial temporal lobe and increased neocortical tau burden compared to healthy controls.
• Baseline tau pathology (tau burden, plasma p-tau 181) and plasma GFAP were negatively associated with synaptic density and predicted longitudinal synaptic loss.
• Plasma GFAP mediated the relationship between tau pathology and synaptic density. Longitudinal synaptic density changes positively correlated with MMSE score changes. Plasma p-tau 181 and GFAP predicted cognitive decline, with tau pathology mediating the effect of plasma GFAP on cognition.

Conclusions:

• Cognitively impaired individuals experience accelerated synaptic loss and tau accumulation over one year.
• Baseline tau pathology and plasma GFAP are significant predictors of synaptic loss and cognitive decline in Alzheimer's disease.
• Findings suggest a synergistic interaction between tau pathology and neuroinflammation, driving synaptic loss and cognitive impairment in AD.