Cerebrospinal fluid biomarkers of axonal and synaptic degeneration in a population-based sample

Background: Neurofilament light (NfL) and neurogranin (Ng) are promising candidate AD biomarkers, reflecting axonal and synaptic damage, respectively. Since there is a need to understand the synaptic and axonal damage in preclinical Alzheimer’s disease (AD), we aimed to determine the cerebrospinal fluid (CSF) levels of NfL and Ng in cognitively unimpaired elderly from the Gothenburg H70 Birth Cohort Studies classified according to the amyloid/tau/neurodegeneration (A/T/N) system. Methods: The sample consisted of 258 cognitively unimpaired older adults (age 70, 129 women and 129 men) from the Gothenburg Birth Cohort Studies. We compared CSF NfL and Ng concentrations in A/T/N groups using Student’s T-test and ANCOVA. Results: CSF NfL concentration was higher in the A−T−N+ group (p=0.001) and the A−T+N+ group (p=0.006) compared with A−T−N−. CSF Ng concentration was higher in the A−T−N+, A−T+N+, A+T−N+, and A+T+N+ groups (p<0.0001) compared with A−T−N−. We found no difference in NfL or Ng concentration in A+ compared with A− (disregarding T− and N− status), whereas those with N+ had higher concentrations of NfL and Ng compared with N− (p<0.0001) (disregarding A− and T− status). Conclusions: CSF NfL and Ng concentrations are increased in cognitively normal older adults with biomarker evidence of tau pathology and neurodegeneration