Plasma and cerebrospinal fluid neurofilament light protein concentrations are differentially associated with biomarker evidence of neurodegeneration in a community‐based population of 70‐year‐olds

Abstract

AbstractBackgroundNeurofilament light protein (NfL) is the best‐established fluid biomarker for general neurodegeneration, predicting poor outcome in cognitive function across neurodegenerative dementias. Currently, there are few studies examining the correlation of plasma and cerebrospinal fluid (CSF) NfL with other fluid and imaging biomarkers for neurodegeneration.MethodThe sample (n= 287) was derived from the Gothenburg H70 Birth cohort 1944 study, conducted in 2014‐2016. CSF NfL, total‐Tau (t‐Tau), phospho‐Tau (p‐Tau), neurogranin, CSF/serum albumin ratio and plasma NfL were measured and brain magnetic resonance imaging (MRI) was conducted. Participants were examined with comprehensive neuropsychiatric and somatic examinations, and dementia was diagnosed according to DSM III criteria. In linear models adjusted for age and sex, NfL was examined in relation to other demographics, cognitive tests, CSF biomarkers and MRI measurements. Sub analysis were also performed on participants with or without β‐Amyloid pathology, defined as a CSF β‐Amyloid 42 ≤ 530 pg/mL.ResultNfL in plasma and CSF presented a moderate correlation (Spearman’s R=0.41, p<0.001). P‐NfL was associated with worse delayed memory recall (p=0.019), smaller hippocampus volume (p=0.001), larger white matter lesion volume (p=0.004), as well as CSF levels of β‐amyloid 42 (p=0.043), β‐amyloid 42/40 (p=0.049), β‐amyloid 42/t‐Tau (p=0.007), CSF NfL (p<0.001) and BMI (p<0.001). CSF NfL was associated with t‐Tau (p=0.001), p‐Tau (p<0.001), neurogranin (p=0.014), albumin ratio (Qalb) (p=0.001), P‐NfL (p<0.001), and BMI (p=0.033). In participants with prevalent β‐amyloid 42 pathology, P‐NfL was associated with β‐amyloid 42 (p=0.009), β‐amyloid 42/40 (p=0.043), β‐amyloid 42/t‐Tau (p=0.010) and CSF NfL (p<0.001). In participants without β‐amyloid 42 pathology, P‐NfL associated with BMI (p<0.001), smaller hippocampus volume (p=0.007) and CSF NfL (p<0.001).ConclusionAlthough CSF NfL and P‐NfL concentrations are correlated, the biomarker measured in the two sample types presents distinct associations with biomarker evidence of AD pathology and neurodegeneration. P‐NfL was associated with several markers that are characteristic of AD, whereas CSF NfL demonstrated more associations with synaptic and neurodegeneration.