Journal
JOURNAL OF ALZHEIMERS DISEASE
Volume 63, Issue 2, Pages 577-590Publisher
IOS PRESS
DOI: 10.3233/JAD-170887
Keywords
Alzheimer's disease; biomarkers; inflammation; pathology
Categories
Funding
- McGill University
- Canada Research Chair award from the government of Canada
- Fonds de Recherche du Quebec-Sante (FRQ-S)
- J.L. Levesque Foundation
- Douglas Mental Health University Institute Foundation
- Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01AG024904]
- DODADNI (Department of Defense) [W81XWH-12-2-0012]
- National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering
- AbbVie
- Alzheimer's Association
- Alzheimer's Drug Discovery Foundation
- Araclon Biotech
- BioClinica, Inc.
- Biogen
- Bristol-Myers Squibb Company
- CereSpir, Inc.
- Cogstate
- Eisai Inc.
- Elan Pharmaceuticals, Inc.
- Eli Lilly and Company
- EuroImmun
- F. Hoffmann-La Roche Ltd
- Genentech, Inc.
- Fujirebio
- GE Healthcare
- IXICO Ltd.
- Janssen Alzheimer Immunotherapy Research & Development, LLC.
- Johnson & Johnson Pharmaceutical Research & Development LLC.
- Lumosity
- Lundbeck
- Merck Co., Inc.
- Meso Scale Diagnostics, LLC.
- NeuroRx Research
- Neurotrack Technologies
- Novartis Pharmaceuticals Corporation
- Pfizer Inc.
- Piramal Imaging
- Servier
- Takeda Pharmaceutical Company
- Transition Therapeutics
- Canadian Institutes for Health Research
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS076794] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [RF1AG053982] Funding Source: NIH RePORTER
Ask authors/readers for more resources
Immune mechanisms may be important in the pathogenesis of Alzheimer's disease (AD). Yet, studies comparing cerebrospinal fluid (CSF) and plasma immune marker levels of healthy and demented individuals have yielded conflicting results. We analyzed CSF from 101 members of the parental history-positive PREVENT-AD cohort of healthy aging adults, and 237 participants without dementia from the initial cohort of the Alzheimer's Disease Neuroimaging Initiative (ADNI-1). Following recent practice, we used the biomarkers total-tau and amyloid-beta(1-42) to allocate participants from each study into four stages of AD pathogenesis: Stage 0 (no abnormality), Stage 1 (reduced amyloid-beta(1-42)), Stage 2 (reduced amyloid-beta(1-42) and increased total-tau), or Suspected Non-Alzheimer Pathology (elevated total-tau only). Investigating the PREVENT-AD participants' CSF assay results for 19 immune/inflammatory markers, we found six that showed a distinct bi-directional relationship with pathogenetic stage. Relative to Stage 0, these were diminished at Stage 1 but strongly increased at Stage 2. Among the ADNI participants (90 healthy controls and 147 with mild cognitive impairment), we found that 23 of 83 available CSF markers also showed this distinct pattern. These results support recent observations that immune activation may become apparent only after the onset of both amyloid and tau pathologies. Unexpectedly, they also suggest that immune marker activity may diminish along with earliest appearance of amyloid-beta plaque pathology. These findings may explain discordant results from past studies, and suggest the importance of characterizing the extent of AD pathology when comparing clinical groups.
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