Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer’s disease (2019) Preische, et al.

[leokitten]

Might increased serum NfL also be a potential biomarker for ME/CFS since it is for Alzheimer’s and other neurological disorders?

https://www.nature.com/articles/s41591-018-0304-3

Neurofilament light chain (NfL) is a promising fluid biomarker of disease progression for various cerebral proteopathies. Here we leverage the unique characteristics of the Dominantly Inherited Alzheimer Network and ultrasensitive immunoassay technology to demonstrate that NfL levels in the cerebrospinal fluid (n = 187) and serum (n = 405) are correlated with one another and are elevated at the presymptomatic stages of familial Alzheimer’s disease. Longitudinal, within-person analysis of serum NfL dynamics (n = 196) confirmed this elevation and further revealed that the rate of change of serum NfL could discriminate mutation carriers from non-mutation carriers almost a decade earlier than cross-sectional absolute NfL levels (that is, 16.2 versus 6.8 years before the estimated symptom onset). Serum NfL rate of change peaked in participants converting from the presymptomatic to the symptomatic stage and was associated with cortical thinning assessed by magnetic resonance imaging, but less so with amyloid-β deposition or glucose metabolism (assessed by positron emission tomography). Serum NfL was predictive for both the rate of cortical thinning and cognitive changes assessed by the Mini–Mental State Examination and Logical Memory test. Thus, NfL dynamics in serum predict disease progression and brain neurodegeneration at the early presymptomatic stages of familial Alzheimer’s disease, which supports its potential utility as a clinically useful biomarker.

 

[leokitten]

One note to add to this interesting paper, is that while they've known that serum NfL isn't a very specific biomarker for Alzheimer's or other neurodegenerative diseases including inflammatory and autoimmune ones, it is a good marker of brain damage occurring due to the disease process. Would be very interesting to know if PwME have elevated serum NfL compared to controls.

 

[Hutan]

Good idea. I despair a bit when I hear that there aren't any good ideas about what to research in ME. To me it seems that there are so many things that could be done.

e.g. Follow people as soon as they are diagnosed with glandular fever. Over the next few years, collect data on physical health, take blood samples and check for stuff*. See if there are any differences between those who get post viral fatigue/ME and those who don't.

*Stuff:

• this NfL for one. Wouldn't it be useful for hypothesis making to have a good indication that there is some brain damage happening - or not happening.
• Eosinophils is another - my daughter was suspected of having appendicitis at ME onset so she had blood tests right at the beginning, unlike my son and I. She had a high level of eosinophils. "Eosinophils help promote inflammation, which plays a beneficial role in isolating and controlling a disease site. But sometimes inflammation may be greater than is necessary". So maybe eosinophil levels are an early indicator of post-viral consequences?
• Other stuff

 

[wigglethemouse]

Follow people as soon as they are diagnosed with glandular fever. Over the next few years, collect data on physical health, take blood samples and check for stuff*. See if there are any differences between those who get post viral fatigue/ME and those who don't.

FYI - Gorden Broderick did evaluate blood from one such study
Cytokine expression profiles of immune imbalance in post-mononucleosis chronic fatigue (2012)

Abstract
Background:
As Chronic Fatigue Syndrome (CFS) has been known to follow Epstein-Bar virus (EBV) and other systemic infections; our objective was to describe differences in immune activation in post-infective CFS (PI-CFS) patients and recovered controls. We studied 301 adolescents prospectively over 24 months following the diagnosis
of monospot-positive infectious mononucleosis (IM). We found an incidence of CFS at 6, 12 and 24 months of 13%,7% and 4% respectively.

Methods:
Using chemiluminescent imaging we measured the concentrations of IL-1a, 1b, 2, 4, 5, 6, 8, 10, 12 (p70),13, 15, 17 and 23, IFN-γ, TNF-α and TNF-β in duplicate plasma samples available in bio-bank from 9 PI-CFS subjects and 12 recovered controls at 24 months post-infection.

Results:
Standard comparative analysis indicated significant differences in IL-8 and 23 across subject groups. In constructing a linear classification model IL-6, 8 and 23 were selected by two different statistical approaches as discriminating features, with IL-1a, IL-2 and IFN-γ also selected in one model or the other. This supported an assignment accuracy of better than 80% at a confidence level of 0.95 into PI-CFS versus recovered controls.

Conclusion:
These results suggest that co-expression patterns in as few as 5 cytokines associated with Th17 function may hold promise as a tool for the diagnosis of post-infectious CFS.