Cerebrospinal fluid (CSF) neurofilament light (NfL) concentration has reproducibly been shown to reflect
neurodegeneration in brain disorders, including Alzheimer’s disease (AD). NfL concentration in blood
correlates with the corresponding CSF levels, but few studies have directly compared the reliability of
these 2 markers in sporadic AD. Herein, we measured plasma and CSF concentrations of NfL in 478
cognitively unimpaired (CU) subjects, 227 patients with mild cognitive impairment, and 113 patients
with AD dementia. We found that the concentration of NfL in CSF, but not in plasma, was increased in
response to Ab pathology in CU subjects. Both CSF and plasma NfL concentrations were increased in
patients with mild cognitive impairment and AD dementia. Furthermore, only NfL in CSF was associated
with reduced white matter microstructure in CU subjects. Finally, in a transgenic mouse model of AD, CSF
NfL increased before serum NfL in response to the development of Ab pathology. In conclusion, NfL in CSF
may be a more reliable biomarker of neurodegeneration than NfL in blood in preclinical sporadic AD
