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F4‐05‐02: COMPARISON OF VARIABLES ASSOCIATED WITH CSF NEUROFILAMENT, TOTAL‐TAU, AND NEUROGRANIN IN A COMMUNITY‐BASED STUDY
Author(s) -
Mielke Michelle M.,
Kern Silke,
Syrjanen Jeremy,
Blennow Kaj,
Zetterberg Henrik,
Knopman David S.,
Jack Clifford R.,
Petersen Ronald C.
Publication year - 2019
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2019.06.4730
Subject(s) - medicine , body mass index , neurogranin , diabetes mellitus , cerebrospinal fluid , oncology , endocrinology , biochemistry , chemistry , protein kinase c , enzyme
Background: Neurofilament light (NfL) is a marker of neuroaxonal injury and has been shown to correlate with cerebrospinal fluid levels of both amyloid and tau. No studies, however, have examined the relationship between plasma NfL and imaging-based measures of amyloid and tau pathology. This study investigates the association between plasma NfL levels and amyloid and tau PET imaging, using data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and the Translational Biomarkers in Aging and Dementia (TRIAD) cohorts. Methods: Longitudinal plasma NfL was measured using an in house Single molecule array methodin 203 ADNI (114 CU, 67 MCI and 22 AD) and in 126 (84 CU, 16 MCI and 26 AD) TRIAD patients with single time point PET imaging ([F]florbetapir and [F]flortaucipir in ADNI; [F]AZD-4694 and [F]MK-6240 in TRIAD) were included. Linear regression was implemented at the voxel level in order to examine the association between plasma NfL and PET-based measures. Results: As compared to CU and MCI subjects, the rate of change in plasma NfL was greater among AD patients. Plasma NfL associations were confined to amyloid PET among CU subjects in both cohorts,and were seen primarily in the posterior cingulate and medial prefrontal cortex. By contrast, widespread associations within lateral temporo-parietal and frontal regions were observed in the AD group, and were specific to tau PET. Conclusions: These findings suggest that plasma NfL may prove an early marker of amyloidrelated neuronal injury in AD, being in turn more closely related to tau-mediated neurodegeneration during the symptomatic course of the disease