Associations between plasma Neurofilament Light Chain (NfL), Sleep Quality and Cognition in individuals with autosomal‐dominant Alzheimer's Disease (ADAD): Findings from the Colombia‐Boston (COLBOS) biomarker study

Abstract

AbstractBackgroundMethods available for in‐vivo diagnosis of Alzheimer's disease (AD) are expensive and invasive. Neurofilament light chain (NfL), a plasma‐based biomarker for neurodegeneration, is a promising marker for early detection in individuals at increased risk. We previously reported that Presenilin1 (PSEN1) E280A carriers have increased levels of plasma NfL relative to non‐carrier family members twenty years before the onset of clinical symptoms. Here, we examined whether baseline levels of plasma NfL predict self‐reported sleep quality and cognition 10 years later in non‐demented PSEN1‐E280A carriers and non‐carriers. MethodsA total of 51 PSEN1‐E280A carriers (mean age = 30.06, SD = 4.63), including 2 mildly impaired carriers and 49 age‐matched non‐carriers (mean age = 35.55, SD = 6.16) from the Colombia‐Boston (COLBOS) longitudinal biomarker study were included. Participants underwent blood sampling at baseline and completed the Pittsburgh Sleep Quality Index (PSQI), Mini Mental State Exam (MMSE), and memory testing (CERAD Word List) at follow‐up approximately 10 years later. Self‐reported sleep quality was assessed by calculating the PSQI score. Plasma NfL concentrations were measured with a single molecule array (Simoa) method. Linear regressions were used to examine associations among NfL levels, sleep quality, and memory.ResultsThere were no group differences, between carriers and non‐carriers, in baseline NfL levels, memory performance, or total PSQI scores (p>0.05). However, carriers had lower MMSE scores than non‐carriers (carriers M=27.90; non‐carriers M=28.47; p = 0.05). Among the entire sample, baseline NfL levels predicted recall scores on the CERAD word list (p = 0.03) and MMSE performance (p = 0.02). Additionally, associations between NfL levels and age trended toward significance (p = 0.06). Sleep quality (PSQI) was not associated with age, memory performance, or NfL levels.ConclusionsPreliminary findings support the hypothesis that plasma NfL levels may predict memory function and overall cognitive status in ADAD. However, our findings suggest that NfL levels may not be associated with self‐reported sleep quality in individuals in prodromal stages of ADAD. Future work using objective sleep metrics and larger samples across the preclinical/prodromal spectrum will allow a more comprehensive examination of these associations.