Cerebrospinal Fluid Neurofilaments Light-Chain Differentiate Patients Affected by Alzheimer’s Disease with Different Rate of Progression (RoP): A Preliminary Study

Alzheimer’s disease (AD) is the most common neurodegenerative disorder and a leading cause of dementia. One major challenge for clinicians is accurately assessing the rate of disease progression (RoP) early in the diagnostic process, which is crucial for patient management and clinical trial stratification. This study evaluated the role of cerebrospinal fluid biomarkers—Aβ42, t-Tau, pTau, Neurogranin (Ng), and Neurofilament light-chain (NF-L)—in predicting RoP at the time of AD diagnosis. We included 56 AD patients and monitored cognitive impairment using MMSE scores at diagnosis and during six-month follow-up visits. RoP scores were calculated based on these assessments. Our correlation analyses revealed significant associations between RoP and pTau, Aβ42/Ng ratio, and NF-L levels. When patients were stratified by median RoP values into low-to-moderate (L-M: <2) and upper-moderate (U-M: >2) groups, those in the U-M group had notably higher CSF NF-L levels compared to the L-M group. Logistic regression analysis further demonstrated that elevated CSF NF-L levels were predictive of a faster RoP. These findings highlight the potential of CSF NF-L as a prognostic biomarker for rapid disease progression in AD. By identifying patients at risk for accelerated cognitive decline, CSF NF-L could significantly enhance early intervention strategies and improve patient management in clinical settings.