TY - JOUR
T1 - Cerebrospinal fluid neurofilament light chain is a marker of aging and white matter damage
AU - Meeker, Karin L.
AU - Butt, Omar H.
AU - Gordon, Brian A.
AU - Fagan, Anne M.
AU - Schindler, Suzanne E.
AU - Morris, John C.
AU - Benzinger, Tammie L.S.
AU - Ances, Beau M.
N1 - Funding Information:
This work was funded by the Bright Focus grant A2021012F (KLM), the Alzheimer's Association grant BAND-19-613876 (BAG), and the National Institute of Health (NIH) grants R01NR012907 (BA), R01NR012657 (BA), R01NR014449 (BA), R01AG052550 (BA), R01AG057680 (BA), P01AG00391 (JCM), P01AG026276 (JCM), P01AG005681 (JCM), and K01AG053474 (BAG), U19AG032438 (BAG), R03AG050921 (SES), K23AG053426 (SES). This work was also supported by the generous support of Barnes-Jewish Hospital , the Washington University Institute of Clinical and Translational Sciences Foundation ( UL1 TR000448 ), the Knight Alzheimer Disease Research Center , the Hope Center for Neurological Disorders , the Paula and Rodger O. Riney Fund, the Daniel J. Brennan MD Fund, and the Fred Simmons and Olga Mohan Fund. The team thanks all participants involved in this study. Support for Florbetapir F18 (18F-AV-45) and Flortaucipir F18 (18F-AV-1451) was provided by Avid Radiopharmaceuticals , a wholly owned subsidiary of Eli Lilly.
Funding Information:
This work was funded by the Bright Focus grant A2021012F (KLM), the Alzheimer's Association grant BAND-19-613876 (BAG), and the National Institute of Health (NIH) grants R01NR012907 (BA), R01NR012657 (BA), R01NR014449 (BA), R01AG052550 (BA), R01AG057680 (BA), P01AG00391 (JCM), P01AG026276 (JCM), P01AG005681 (JCM), and K01AG053474 (BAG), U19AG032438 (BAG), R03AG050921 (SES), K23AG053426 (SES). This work was also supported by the generous support of Barnes-Jewish Hospital, the Washington University Institute of Clinical and Translational Sciences Foundation (UL1 TR000448), the Knight Alzheimer Disease Research Center, the Hope Center for Neurological Disorders, the Paula and Rodger O. Riney Fund, the Daniel J. Brennan MD Fund, and the Fred Simmons and Olga Mohan Fund. The team thanks all participants involved in this study. Support for Florbetapir F18 (18F-AV-45) and Flortaucipir F18 (18F-AV-1451) was provided by Avid Radiopharmaceuticals, a wholly owned subsidiary of Eli Lilly.
Publisher Copyright:
© 2022
PY - 2022/5
Y1 - 2022/5
N2 - Background: Cerebrospinal fluid (CSF) neurofilament light chain (NfL) reflects neuro-axonal damage and is increasingly used to evaluate disease progression across neurological conditions including Alzheimer disease (AD). However, it is unknown how NfL relates to specific types of brain tissue. We sought to determine whether CSF NfL is more strongly associated with total gray matter, white matter, or white matter hyperintensity (WMH) volume, and to quantify the relative importance of brain tissue volume, age, and AD marker status (i.e., APOE genotype, brain amyloidosis, tauopathy, and cognitive status) in predicting CSF NfL. Methods: 419 participants (Clinical Dementia Rating [CDR] Scale > 0, N = 71) had CSF, magnetic resonance imaging (MRI), and neuropsychological data. A subset had amyloid positron emission tomography (PET) and tau PET. Pearson correlation analysis was used to determine the association between CSF NfL and age. Multiple regression was used to determine which brain volume (i.e., gray, white, or WMH volume) most strongly associated with CSF NfL. Stepwise regression and dominance analyses were used to determine the individual contributions and relative importance of brain volume, age, and AD marker status in predicting CSF NfL. Results: CSF NfL increased with age (r = 0.59, p < 0.001). Elevated CSF NfL was associated with greater total WMH volume (p < 0.001), but not gray or white matter volume (p's > 0.05) when considered simultaneously. Age and WMH volume were consistently more important (i.e., have greater R2 values) than AD markers when predicting CSF NfL. Conclusions: CSF NfL is a non-specific marker of aging and white matter integrity with limited sensitivity to specific markers of AD. CSF NfL likely reflects processes associated with cerebrovascular disease.
AB - Background: Cerebrospinal fluid (CSF) neurofilament light chain (NfL) reflects neuro-axonal damage and is increasingly used to evaluate disease progression across neurological conditions including Alzheimer disease (AD). However, it is unknown how NfL relates to specific types of brain tissue. We sought to determine whether CSF NfL is more strongly associated with total gray matter, white matter, or white matter hyperintensity (WMH) volume, and to quantify the relative importance of brain tissue volume, age, and AD marker status (i.e., APOE genotype, brain amyloidosis, tauopathy, and cognitive status) in predicting CSF NfL. Methods: 419 participants (Clinical Dementia Rating [CDR] Scale > 0, N = 71) had CSF, magnetic resonance imaging (MRI), and neuropsychological data. A subset had amyloid positron emission tomography (PET) and tau PET. Pearson correlation analysis was used to determine the association between CSF NfL and age. Multiple regression was used to determine which brain volume (i.e., gray, white, or WMH volume) most strongly associated with CSF NfL. Stepwise regression and dominance analyses were used to determine the individual contributions and relative importance of brain volume, age, and AD marker status in predicting CSF NfL. Results: CSF NfL increased with age (r = 0.59, p < 0.001). Elevated CSF NfL was associated with greater total WMH volume (p < 0.001), but not gray or white matter volume (p's > 0.05) when considered simultaneously. Age and WMH volume were consistently more important (i.e., have greater R2 values) than AD markers when predicting CSF NfL. Conclusions: CSF NfL is a non-specific marker of aging and white matter integrity with limited sensitivity to specific markers of AD. CSF NfL likely reflects processes associated with cerebrovascular disease.
KW - Aging
KW - Alzheimer disease
KW - Cerebrospinal fluid
KW - Cerebrovascular disease
KW - Neurofilament light
KW - White matter
UR - http://www.scopus.com/inward/record.url?scp=85124873468&partnerID=8YFLogxK
U2 - 10.1016/j.nbd.2022.105662
DO - 10.1016/j.nbd.2022.105662
M3 - Article
C2 - 35167933
AN - SCOPUS:85124873468
VL - 166
JO - Neurobiology of Disease
JF - Neurobiology of Disease
SN - 0969-9961
M1 - 105662
ER -