CSF total tau as a proxy of synaptic degeneration

Area of Science:

• Neuroscience
• Biomarker Research
• Alzheimer's Disease Pathophysiology

Background:

• Cerebrospinal fluid (CSF) total tau (t-tau) is a biomarker for neuronal degeneration in Alzheimer's disease (AD).
• Previous research indicates CSF t-tau correlates with synaptic dysfunction markers like neurogranin (Ng).

Purpose of the Study:

• To compare the association between CSF t-tau and synaptic versus axonal/neuronal degeneration biomarkers.
• To investigate these associations in both cognitively unimpaired and impaired individuals across two independent cohorts.

Main Methods:

• Analysis of CSF t-tau levels in relation to synaptic degeneration biomarkers (e.g., Ng, SNAP25).
• Comparison with axonal/neuronal degeneration biomarkers (e.g., neurofilament light chain protein [NfL]) and brain atrophy.
• Statistical analysis of biomarker correlations and variance explained in independent cohorts.

Main Results:

• CSF t-tau showed a stronger correlation with synaptic degeneration biomarkers than with axonal/neuronal degeneration biomarkers.
• Synaptic biomarkers explained a larger proportion of the variance in CSF t-tau levels compared to neurodegeneration biomarkers.
• Elevated CSF t-tau was observed in individuals with synaptic biomarker abnormalities, but not solely with neurodegeneration biomarker abnormalities.

Conclusions:

• CSF total tau (t-tau) is a more sensitive indicator of synaptic degeneration than axonal or general neuronal degeneration in Alzheimer's disease.
• The findings suggest CSF t-tau may serve as a closer proxy for synaptic damage in AD.
• This highlights the importance of considering synaptic integrity when interpreting CSF t-tau levels in AD research.