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Low plasma neurofilament light levels associated with raised cortical microglial activation suggest inflammation acts to protect prodromal Alzheimer’s disease

Lookup NU author(s): Professor David BrooksORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


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 remodeling synapses. Our aim was to determine whether the cortical inflammation/microglial activation load, measured with the translocator protein marker 11C-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 11C-(R)-PK11195 PET, structural and diffusion magnetic resonance imaging, and levels of their plasma NfL measured. Correlation analyses were performed using surface based cortical area statistics. Results: Surface based cortical statistics localised areas in MCI cases where levels of brain inflammation correlated inversely with plasma NfL levels. These areas were localised in the frontal, cingulate, parietal, precuneus, occipital, and sensorimotor cortices[PP1] . Brain inflammation correlated negatively with mean diffusivity (MD) of water following a similar pattern. Conclusion: We conclude that an inverse correlation between levels of inflammation in cortical areas and plasma NfL levels indicate 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 provide 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.

Publication metadata

Author(s): Parbo P, Madsen LS, Ismail R, Zetterberg H, Blennow K, Eskildsen SF, Jensen TV, Brooks DJ

Publication type: Article

Publication status: Published

Journal: Alzheimer's Research and Therapy

Year: 2020

Volume: 12

Online publication date: 02/01/2020

Acceptance date: 23/12/2019

Date deposited: 23/12/2019

ISSN (electronic): 1758-9193

Publisher: BioMed Central Ltd.


DOI: 10.1186/s13195-019-0574-0


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Funder referenceFunder name
Aarhus University Research Foundation
Danish Council of Independent Research
European Research Council
Lundbeck Foundation
Swedish Research Council
Olav Thon Foundation