Serum neurofilament light level in the clinical diagnosis of Chinese patients with Alzheimer’s disease

Abstract

AbstractBackgroundBiomarkers are much needed to assist the clinicians in the diagnosis of Alzheimer disease (AD). Neurofilament light chain (NfL) was reported as a promising blood biomarker to detect neurodegeneration in Alzheimer's disease (AD) in previous Caucasian studies. In this study, we aimed to evaluate the diagnostic accuracy of the serum neurofilament light (NfL) level in the clinical diagnosis of Chinese patients with Alzheimer’s Disease.MethodWe performed a nested case‐control study on Alzheimer’s disease patients and cognitively normal older adults, who were recruited in a prospective cohort on aging and dementia in Hong Kong in 2004‐2005. Alzheimer’s disease (AD) was diagnosed in accordance to the National Institute of Neurological and Communicative Disorders and Stroke / Alzheimer’s Disease and Related Disorders Association (NINCDS‐ADRDA) criteria. Normal control subjects had normal cognition without cognitive complaint or impairment on assessment. Blood samples were immediately processed and serum samples were stored in cryotubes in ‐80°C freezers. The serum samples of subjects were retrieved for assay of serum neurofilaments light (NfL) chain assays, using a highly sensitive single molecule array assay (SIMOA) with the Quanterix SIMOA HD‐1 Analyzer. For matching of APOE4 (with 1 or 2 copies of APOE4) status, we randomly selected 50% APOE4 positive and 50% APOE4 negative subjects.ResultThree subjects who had inadequate serum were excluded. Finally, 149 subjects (75 AD and 74 normal control) subjects were included‐ (Table). AD subjects were significantly older (p<0.001). less educated (p<0.001), and had lower Mini‐Mental State Examination (MMSE) scores (p<0.001). Age showed a positive correlation with the serum NfL level (r=0.56, p<0.001). Multivariate analyses with general linear model showed the serum NfL level was significantly higher in AD than normal control, after adjustment for age, sex and APOE. Receiver Operating Characteristic (ROC) curve analyses showed the Area‐Under‐Curve (AUC) was 0.859 (p<0.001). The optimal cut‐off of the serum NfL level for the diagnosis of AD was >17.31 pg/ml, with sensitivity and specificity of 89% and 73% respectively.ConclusionIn this study, we found the serum NfL level is a useful blood biomarker for the diagnosis of Alzheimer’s Disease in Chinese persons.