Plasma and CSF NfL are differentially associated with biomarker evidence of neurodegeneration in a community‐based sample of 70‐year‐olds

Neurofilament light protein (NfL) in cerebrospinal fluid (CSF) and plasma (P) are suggested to be interchangeable markers of neurodegeneration. However, evidence is scarce from community‐based samples. NfL was examined in a small‐scale sample of 287 individuals from the Gothenburg H70 Birth cohort 1944 study, using linear models in relation to CSF and magnetic resonance imaging (MRI) biomarker evidence of neurodegeneration. CSF‐NfL and P‐NfL present distinct associations with biomarker evidence of Alzheimer's disease (AD) pathology and neurodegeneration. P‐NfL was associated with several markers that are characteristic of AD, including smaller hippocampal volumes, amyloid beta (Aβ)(42), Aβ(42/40), and Aβ(42)/t‐tau (total tau). CSF‐NfL demonstrated associations with measures of synaptic and neurodegeneration, including t‐tau, phosphorylated tau (p‐tau), and neurogranin. Our findings suggest that P‐NfL and CSF‐NfL may exert different effects on markers of neurodegeneration in a small‐scale community‐based sample of 70‐year‐olds.