CSF neurofilament light may predict progression from amnestic mild cognitive impairment to Alzheimer's disease dementia

Bryant Lim; Gøril Rolfseng Grøntvedt; Pradeepthi Bathala; Shraddha S Kale; Christopher T Campbell; Martin Stengelin; Sigrid Botne Sando; Ioannis Prassas; Eleftherios P Diamandis; Geir Bråthen

doi:10.1016/j.neurobiolaging.2021.07.013

CSF neurofilament light may predict progression from amnestic mild cognitive impairment to Alzheimer's disease dementia

Neurobiol Aging. 2021 Nov:107:78-85. doi: 10.1016/j.neurobiolaging.2021.07.013. Epub 2021 Jul 24.

Affiliations

¹ Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Canada.
² Department of Neurology and Clinical Neurophysiology, University Hospital of Trondheim, Trondheim, Norway; Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.
³ Meso Scale Diagnostics, LLC., Rockville, MD, USA.
⁴ Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada; Department of Clinical Biochemistry, University Health Network, Toronto, Canada.
⁵ Department of Neurology and Clinical Neurophysiology, University Hospital of Trondheim, Trondheim, Norway; Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway. Electronic address: geir.brathen@ntnu.no.

PMID: 34403936
DOI: 10.1016/j.neurobiolaging.2021.07.013

Abstract

Neurofilament light (NfL) is a promising biomarker of neurodegeneration in Alzheimer's disease (AD). In this study, cerebrospinal fluid (CSF) NfL was measured in a 24-month longitudinal cohort consisting of control (n = 52), amnestic mild cognitive impairment (aMCI) (n = 55), and probable AD dementia (n = 28) individuals. The cohort was reevaluated after 6-10 years. Baseline CSF NfL was significantly elevated in aMCI and probable AD dementia groups compared to controls (p < 0.0001). CSF NfL was significantly lower in stable aMCI patients compared to aMCI patients who converted to probable AD dementia within the 24-month period (p = 0.004). Substituting T-tau for NfL in the core AD biomarkers model (Aβ42/P-tau/T-tau) did not improve ability to separate control and AD, or stable and converter aMCI patients. Our results support that elevated CSF NfL could predict progression in aMCI patients, but its utility cannot improve the core AD biomarkers.

Keywords: Alzheimer's disease; Biomarker; Cerebrospinal fluid; Neurofilament Light; Predict Progression.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Alzheimer Disease / diagnosis*
Alzheimer Disease / etiology*
Biomarkers / cerebrospinal fluid
Cognitive Dysfunction / diagnosis*
Cognitive Dysfunction / etiology*
Disease Progression
Female
Humans
Longitudinal Studies
Male
Middle Aged
Neurofilament Proteins / cerebrospinal fluid*
Predictive Value of Tests
Time Factors

Substances

Biomarkers
Neurofilament Proteins
neurofilament protein L

Grants and funding

U24 AI118663/AI/NIAID NIH HHS/United States