Biomarkers.

Area of Science:

• Neuroscience
• Biomarker Research
• Alzheimer's Disease Research

Background:

• Alzheimer's disease (AD) involves tau and amyloid pathology in synapses, potentially causing synaptic loss.
• Plasma phosphorylated tau at 217 (pTau217) is a neuron-derived biomarker for AD pathology.
• Understanding the link between pTau217 and synaptic changes is crucial for early AD detection and intervention.

Purpose of the Study:

• To investigate the relationship between plasma pTau217 levels and synaptic density in medial-temporal brain regions.
• To determine if plasma pTau217 is associated with synaptic density and cognitive impairment in individuals at risk for AD.

Main Methods:

• Analysis of plasma pTau217 levels and [C-11]UCB-J PET scans in 50 participants.
• Quantification of synaptic density using Logan Graphical Analysis and identification of regions of interest (ROIs).
• Multiple regression analysis to assess associations between plasma pTau217, cognitive status, synaptic density, and amyloid positivity, controlling for age.

Main Results:

• Higher plasma pTau217 levels were associated with higher synaptic density in the entorhinal cortex (p=0.02).
• Cognitive impairment correlated with lower synaptic density in the entorhinal cortex (p=0.02) and hippocampus (p<0.05).
• Effect sizes for these associations ranged from small-to-moderate to moderate-to-large.

Conclusions:

• The observed relationship between pTau217 and synaptic density may reflect an early compensatory mechanism in response to AD pathology.
• Most participants were cognitively unimpaired, suggesting these findings represent an early disease stage.
• Longitudinal studies are planned to track the progression of plasma pTau217 and synaptic density over time.