Journal
ANNALS OF NEUROLOGY
Volume 83, Issue 3, Pages 544-552Publisher
WILEY
DOI: 10.1002/ana.25172
Keywords
-
Categories
Funding
- Biomarkers across Neurodegenerative Diseases 2 program of the Michael J. Fox Foundation for Parkinson's Research
- Alzheimer's Association
- Alzheimer's Research United Kingdom
- Weston Brain Institute
- NIH National Institute on Aging (NIA) [P30028383]
- Intramural Research Program of the NIH NIA
Ask authors/readers for more resources
ObjectiveAstrocytes fulfill neuronal trophic roles normally, but are transformed in Alzheimer disease (AD) into A1-type reactive astrocytes that may destroy neurons through unknown mechanisms. MethodsTo investigate astrocyte inflammatory mechanisms, astrocyte-derived exosomes (ADEs) were isolated immunochemically from plasma samples of AD patients and matched controls for enzyme-linked immunosorbent assay quantification of complement proteins. ResultsADE levels of C1q, C4b, C3d, factor B, factor D, Bb, C3b, and C5b-C9 terminal complement complex, but not mannose-binding lectin, normalized by the CD81 exosome marker were significantly higher for AD patients (n=28) than age- and gender-matched controls (all p<0.0001). ADE normalized levels of interleukin (IL)-6, tumor necrosis factor-, and IL-1 were significantly higher for AD patients than controls, but there was greater overlap between the two groups than for complement proteins. Mean ADE levels of complement proteins for AD patients in a longitudinal study were significantly higher (n=16, p<0.0001) at the AD2 stage of moderate dementia than at the AD1 preclinical stage 5 to 12 years earlier, which were the same as for controls. ADE levels of complement regulatory proteins CD59, CD46, decay-accelerating factor (DAF), and complement receptor type 1, but not factor I, were significantly lower for AD patients than controls (p<0.0001 for CD59 and DAF), were diminished by the AD1 stage, and were further decreased at the AD2 stage. InterpretationADE complement effector proteins in AD are produced by dysregulated systems, attain higher levels than in controls, and may potentially damage neurons in the late inflammatory phase of AD. Ann Neurol 2018;83:544-552
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available