Plasma neurofilament light levels predict poor memory and cognition, but not sleep, in prodromal Alzheimer’s stages

Preliminary data from the Columbia-Boston Longitudinal Biomarker Study (COLBOS) showed that in patients with autosomal dominant Alzheimer’s disease (ADAD), plasma neurofilament light (NfL) levels were associated with memory function and overall health, but not with the sleep quality, were associated.¹

Using a cohort of 51 non-demented presenillin1 (PSEN1) E280A carriers and 49 age-matched non-carriers, baseline NfL levels predicted recall scores in CERAD word delay (P = .03) and Mini Mental State Examination (MMSE) performance (P = 0.02). The findings were presented at the 2022 Alzheimer’s Association International Conference July 31-August 4 in San Diego, California, by lead researcher Yakeel T. Quiroz, PhD, neuropsychologist, Massachusetts General Hospital.

COLBOS, a collaborative project between the Universidad de Antioquia Columbia and Massachusetts General Hospital in Boston, works with the families of approximately 6,000 people in Antioquia, Columbia, who are approximately 1,500 carriers of PSEN1 E280A. These carriers are genetically destined to develop early-onset AD with nearly 100% certainty and have a well-characterized disease course with mild cognitive impairment occurring at a median age of 44 years and dementia at 49 years.²

NfL, a promising biomarker of neurodegeneration, was measured using a single molecule array (SIMOA) and did not differ between groups at baseline. In addition, there were no group differences between carriers and non-carriers in baseline memory performance or total Pittsburgh Sleep Quality Index (PSQI) scores (P >.05). However, carriers had lower MMSE scores (carrier: mean 27.90; non-carrier: mean 28.47; P = 0.02). Patients were followed up for a period of 10 years, with investigators performing Student’s ρ-correlation analyzes according to Mann-Whitney and Pearson.¹

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After 10 years of follow-up, results suggested that NfL predicts memory function and overall cognitive status; However, sleep quality assessed using the PSQI was not associated with age, memory, or NfL scores. Specifically, the researchers observed associations between NfL scores and age that trended toward significance (P = 0.06). “Future work using objective sleep metrics and larger samples across the preclinical/prodromal spectrum will allow for a more comprehensive examination of these associations,” the study researchers wrote.

The findings build on a study published in 2020 in which Quiroz et al. a cohort of 1070 studied PSEN1 E280A mutation carriers and 1074 non-carriers to assess the relationship between plasma NfLs and age and determine the earliest age at which NfL separates between mutation carriers and non-carriers. Results showed that plasma NfL increased with age in both groups (P <0.01) and began to differentiate at age 22 years - 22 years before the estimated mean age of 44 years at onset of mild cognitive impairment - although the ability of plasma NfL to discriminate between carriers and non-carriers is only close to age from a high sensitivity reached clinical onset.³

Regarding the future implications of these findings, Quirez et al. wrote: “The emerging evidence supports the promise of plasma NfL and other blood-based biomarkers in detecting and tracking AD and related disorders, assessing risk modifiers for these neurodegenerative diseases.” and the evaluation of disease-modifying treatments. Additional studies are needed to clarify the generalizability of the results, the relationship between various blood-based and other biomarkers of AD and related diseases, and the role of these peripheral markers of neurodegeneration in the evaluation of interventions to treat and prevent these disorders as well as implications for their future use in clinical settings.”³

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1. D. Noriega, E. Pardilla-Delgado, AY Baena et al. Associations between plasma neurofilament light chain (NfL), sleep quality, and cognition in individuals with autosomal dominant Alzheimer’s disease (ADAD): results from the Columbia-Boston (COLBOS) biomarker study. Presented at: 2022 Alzheimer’s Association International Conference; July 31 – August 4; San Diego, CA 67817
2. Columbia-Boston Autosomal Dominant Alzheimer’s Disease Biomarker Study. Massachusetts General Hospital. https://mapp.mgh.harvard.edu/projects/colbos/. Retrieved August 2, 2022.

3. Quiroz YT, Zetterberg H, Reiman EM, et al. Plasma neurofilament light chain in the presenilin-1 E280A autosomal dominant Alzheimer’s disease kindred: a cross-sectional and longitudinal cohort study: a cross-sectional and longitudinal cohort study. Lancet Neurol. 2020;19(6):513-521.