CSF Neurofilament Light Chain (NfL) levels best predict cortical atrophy and cognitive decline in early-onset Alzheimer's disease.

Early-onset Alzheimer's disease (EOAD) presents unique diagnostic and prognostic challenges, often differing from late-onset forms in its genetic underpinnings and clinical progression. While cerebrospinal fluid (CSF) biomarkers like amyloid-beta and tau are established indicators of neurodegeneration in general Alzheimer's disease (AD), their specific utility in tracking neurodegeneration and predicting cognitive decline in EOAD has remained less clear. Understanding which biomarkers correlate with structural brain changes, such as cortical atrophy, is crucial for developing more precise diagnostic tools and monitoring disease progression in this specific patient population.

Researchers investigated the relationship between CSF biomarkers and cortical atrophy in 80 EOAD patients. They first examined correlations between eight different CSF biomarker levels and decreases in cortical thickness within the established EOAD cortical atrophy signature. Biomarkers showing significant correlations were then subjected to a multiple regression analysis to identify the strongest predictors. The study also assessed the combined contributions of EOAD signature atrophy and CSF biomarker levels to the severity of cognitive impairment using a multiple regression model.

The study identified that four of the eight CSF biomarkers examined correlated significantly with EOAD signature atrophy. Through stepwise regression analyses, CSF neurofilament light chain (NfL) levels emerged as the single best predictor of EOAD signature atrophy. This indicates a strong link between neuronal damage, as reflected by NfL, and structural brain changes in EOAD. When considering cognitive impairment, a combined model proved most robust:

EOAD signature atrophy combined with CSF NfL levels explained more variance in cognitive impairment than either factor alone. This suggests that while both atrophy and NfL are important, their synergistic effect provides a more comprehensive understanding of cognitive decline in EOAD patients. The abstract did not provide specific quantitative values such as correlation coefficients, p-values, or explained variance percentages for these findings.