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Association Between Longitudinal Plasma Neurofilament Light and Neurodegeneration in Patients With Alzheimer Disease
Mattsson N, Cullen NC, Andreasson U, Zetterberg H, Blennow K.. JAMA neurology, 2019-07-01
Topic: Amyloid, tau and blood-test diagnosis
Importance Plasma neurofilament light (NfL) has been suggested as a noninvasive biomarker to monitor neurodegeneration in Alzheimer disease (AD), but studies are lacking. Objective To examine whether longitudinal plasma NfL levels are associated with other hallmarks of AD. Design, setting, and participants This North American cohort study used data from 1583 individuals in the multicenter Alzheimer's Disease Neuroimaging Initiative study from September 7, 2005, through June 16, 2016. Patients were eligible for inclusion if they had NfL measurements. Annual plasma NfL samples were collected for up to 11 years and were analyzed in 2018. Exposures Clinical diagnosis, Aβ and tau cerebrospinal fluid (CSF) biomarkers, imaging measures (magnetic resonance imaging and fluorodeoxyglucose-positron emission tomography), and tests on cognitive scores. Main outcomes and measures The primary outcome was the association between baseline exposures (diagnosis, CSF biomarkers, imaging measures, and cognition) and longitudinal plasma NfL levels, analyzed by an ultrasensitive assay. The secondary outcomes were the associations between a multimodal classification scheme with Aβ, tau, and neurodegeneration (ie, the ATN system) and plasma NfL levels and between longitudinal changes in plasma NfL levels and changes in the other measures. Results Of the included 1583 participants, 716 (45.2%) were women, and the mean (SD) age was 72.9 (7.1) years; 401 had no cognitive impairment, 855 had mild cognitive impairment, and 327 had AD dementia. The NfL level was increased at baseline in patients with mild cognitive impairment and AD dementia (mean levels: cognitive unimpairment, 32.1 ng/L; mild cognitive impairment, 37.9 ng/L; and AD dementia, 45.9 ng/L; P Conclusions and relevance The findings suggest that plasma NfL can be used as a noninvasive biomarker associated with neurodegeneration in patients with AD and may be useful to monitor effects in trials of disease-modifying drugs.
Key findings
- Objective To examine whether longitudinal plasma NfL levels are associated with other hallmarks of AD.
- Results Of the included 1583 participants, 716 (45.2%) were women, and the mean (SD) age was 72.9 (7.1) years; 401 had no cognitive impairment, 855 had mild cognitive impairment, and 327 had AD dementia.
- The NfL level was increased at baseline in patients with mild cognitive impairment and AD dementia (mean levels: cognitive unimpairment, 32.1 ng/L; mild cognitive impairment, 37.9 ng/L; and AD dementia, 45.9 ng/L; P < .001) and increased in all diagnostic groups, with the greatest increase in patients with AD dementia.
Why it matters
In this cohort, higher plasma neurofilament light levels were seen in people with mild cognitive impairment and Alzheimer's dementia than in those without cognitive impairment. This suggests plasma NfL may be useful as a noninvasive marker of neurodegeneration, but the study does not show that measuring it changes treatment, prevention or cure.
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Study details
- Study designcohort study
- Participants1,583
- Effect size45.2%
- Evidence strengthModerate
How this study scored 76/100
Published in a leading specialty journal, and it is a cohort study following people over time. Scored zero for randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (JAMA neurology) |
| Journal's citation record | 2 / 4 | JAMA Neurology: journal h-index 235 (OpenAlex, 2026-10-29) |
| Study design | 7 / 12 | A cohort study following people over time |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2019 — within 10 year(s) of the newest study here |
| Sample size | 3 / 4 | 1,583 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 722 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 80.2 citations a year over 9 year(s) since 2019 |
| Impact for its field and year | 6 / 6 | Cited 56.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 77 other studies in this library |
| Still being cited | 4 / 4 | Cited 299 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Kaj Blennow: h-index 220 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University College London: institution h-index 2,029 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 9 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 31009028) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 76 / 100 | — |
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Read the original
- DOI: 10.1001/jamaneurol.2019.0765
- PubMed: 31009028
- Original source →
- Free full text: PubMed Central →
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
APA 7th
Mattsson, N., Cullen, N. C., Andreasson, U., Zetterberg, H., & Blennow, K. (2019). Association Between Longitudinal Plasma Neurofilament Light and Neurodegeneration in Patients With Alzheimer Disease. JAMA neurology. https://doi.org/10.1001/jamaneurol.2019.0765
Vancouver
Mattsson N, Cullen NC, Andreasson U, Zetterberg H, Blennow K. Association Between Longitudinal Plasma Neurofilament Light and Neurodegeneration in Patients With Alzheimer Disease. JAMA neurology. 2019. doi:10.1001/jamaneurol.2019.0765. PMID: 31009028.
BibTeX
@article{mattsson2019-31009028,
author = {Mattsson, N. and Cullen, N. C. and Andreasson, U. and Zetterberg, H. and Blennow, K.},
title = {{Association Between Longitudinal Plasma Neurofilament Light and Neurodegeneration in Patients With Alzheimer Disease}},
journal = {JAMA neurology},
year = {2019},
doi = {10.1001/jamaneurol.2019.0765},
pmid = {31009028},
url = {https://doi.org/10.1001/jamaneurol.2019.0765}
}
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