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Low plasma neurofilament light levels associated with raised cortical microglial activation suggest inflammation acts to protect prodromal Alzheimer's disease
Parbo P, Madsen LS, Ismail R, Zetterberg H, Blennow K, Eskildsen SF, Vorup-Jensen T, Brooks DJ.. Alzheimer's research & therapy, 2020-01-02
Topic: Brain proteins, microglia and lab models
Background Plasma and cerebrospinal fluid levels of neurofilament light (NfL), a marker of axonal degeneration, have previously been reported to be raised in patients with clinically diagnosed Alzheimer's disease (AD). Activated microglia, an intrinsic inflammatory response to brain lesions, are also known to be present in a majority of Alzheimer or mild cognitive impaired (MCI) subjects with raised β-amyloid load on their positron emission tomography (PET) imaging. It is now considered that the earliest phase of inflammation may be protective to the brain, removing amyloid plaques and remodelling synapses. Our aim was to determine whether the cortical inflammation/microglial activation load, measured with the translocator protein marker 11 C-PK11195 PET, was correlated with plasma NfL levels in prodromal and early Alzheimer subjects. Methods Twenty-seven MCI or early AD cases with raised cortical β-amyloid load had 11 C-(R)-PK11195 PET, structural and diffusion magnetic resonance imaging, and levels of their plasma NfL measured. Correlation analyses were performed using surface-based cortical statistics. Results Statistical maps localised areas in MCI cases where levels of brain inflammation correlated inversely with plasma NfL levels. These areas were localised in the frontal, parietal, precuneus, occipital, and sensorimotor cortices. Brain inflammation correlated negatively with mean diffusivity (MD) of water with regions overlapping. Conclusion We conclude that an inverse correlation between levels of inflammation in cortical areas and plasma NfL levels indicates that microglial activation may initially be protective to axons in AD. This is supported by the finding of an inverse association between cortical water diffusivity and microglial activation in the same regions. Our findings suggest a rationale for stimulating microglial activity in early and prodromal Alzheimer cases-possibly using immunotherapy. Plasma NfL levels could be used as a measure of the protective efficacy of immune stimulation and for monitoring efficacy of putative neuroprotective agents.
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APA 7th
Parbo, P., Madsen, L. S., Ismail, R., Zetterberg, H., Blennow, K., Eskildsen, S. F., et al. (2020). Low plasma neurofilament light levels associated with raised cortical microglial activation suggest inflammation acts to protect prodromal Alzheimer's disease. Alzheimer's research & therapy. https://doi.org/10.1186/s13195-019-0574-0
Vancouver
Parbo P, Madsen LS, Ismail R, Zetterberg H, Blennow K, Eskildsen SF, et al. Low plasma neurofilament light levels associated with raised cortical microglial activation suggest inflammation acts to protect prodromal Alzheimer's disease. Alzheimer's research & therapy. 2020. doi:10.1186/s13195-019-0574-0. PMID: 31898549.
BibTeX
@article{parbo2020-31898549,
author = {Parbo, P. and Madsen, L. S. and Ismail, R. and Zetterberg, H. and Blennow, K. and Eskildsen, S. F. and Vorup-Jensen, T. and Brooks, D. J.},
title = {{Low plasma neurofilament light levels associated with raised cortical microglial activation suggest inflammation acts to protect prodromal Alzheimer's disease}},
journal = {Alzheimer's research \& therapy},
year = {2020},
doi = {10.1186/s13195-019-0574-0},
pmid = {31898549},
url = {https://doi.org/10.1186/s13195-019-0574-0}
}
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Key findings
- Results Statistical maps localised areas in MCI cases where levels of brain inflammation correlated inversely with plasma NfL levels.
- Conclusion We conclude that an inverse correlation between levels of inflammation in cortical areas and plasma NfL levels indicates that microglial activation may initially be protective to axons in AD.
- Our findings suggest a rationale for stimulating microglial activity in early and prodromal Alzheimer cases-possibly using immunotherapy.
Why it matters
In 27 people with mild cognitive impairment or early Alzheimer disease, higher brain inflammation in some cortical areas was linked to lower plasma neurofilament light, which the authors suggest means microglial activation may initially protect axons. They propose that stimulating microglial activity in early disease could be worth testing, but this was an observational study and no treatment was given.
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Study details
- Evidence strengthLow
How this study scored 41/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Alzheimer's research & therapy) |
| Journal's citation record | 1 / 4 | Alzheimer s Research & Therapy: journal h-index 146 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2020 — within 10 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 3 / 7 | Cited 33 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 4.1 citations a year over 8 year(s) since 2020 |
| Impact for its field and year | 2 / 6 | Cited 1.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 1 / 4 | Cited 11 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author David James Brooks: h-index 158 (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 31898549) |
| Free to read | 2 / 2 | Free to read |
| Total | 41 / 100 | — |
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