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An integrative multi-omics approach reveals new central nervous system pathway alterations in Alzheimer's disease
Clark C, Dayon L, Masoodi M, Bowman GL, Popp J.. Alzheimer's research & therapy, 2021-04-01
Topic: Amyloid, tau and blood-test diagnosis
Background Multiple pathophysiological processes have been described in Alzheimer's disease (AD). Their inter-individual variations, complex interrelations, and relevance for clinical manifestation and disease progression remain poorly understood. We hypothesize that specific molecular patterns indicating both known and yet unidentified pathway alterations are associated with distinct aspects of AD pathology. Methods We performed multi-level cerebrospinal fluid (CSF) omics in a well-characterized cohort of older adults with normal cognition, mild cognitive impairment, and mild dementia. Proteomics, metabolomics, lipidomics, one-carbon metabolism, and neuroinflammation related molecules were analyzed at single-omic level with correlation and regression approaches. Multi-omics factor analysis was used to integrate all biological levels. Identified analytes were used to construct best predictive models of the presence of AD pathology and of cognitive decline with multifactorial regression analysis. Pathway enrichment analysis identified pathway alterations in AD. Results Multi-omics integration identified five major dimensions of heterogeneity explaining the variance within the cohort and differentially associated with AD. Further analysis exposed multiple interactions between single 'omics modalities and distinct multi-omics molecular signatures differentially related to amyloid pathology, neuronal injury, and tau hyperphosphorylation. Enrichment pathway analysis revealed overrepresentation of the hemostasis, immune response, and extracellular matrix signaling pathways in association with AD. Finally, combinations of four molecules improved prediction of both AD (protein 14-3-3 zeta/delta, clusterin, interleukin-15, and transgelin-2) and cognitive decline (protein 14-3-3 zeta/delta, clusterin, cholesteryl ester 27:1 16:0 and monocyte chemoattractant protein-1). Conclusions Applying an integrative multi-omics approach we report novel molecular and pathways alterations associated with AD pathology. These findings are relevant for the development of personalized diagnosis and treatment approaches in AD.
Key findings
- We hypothesize that specific molecular patterns indicating both known and yet unidentified pathway alterations are associated with distinct aspects of AD pathology.
- Results Multi-omics integration identified five major dimensions of heterogeneity explaining the variance within the cohort and differentially associated with AD.
- Enrichment pathway analysis revealed overrepresentation of the hemostasis, immune response, and extracellular matrix signaling pathways in association with AD.
- Conclusions Applying an integrative multi-omics approach we report novel molecular and pathways alterations associated with AD pathology.
- These findings are relevant for the development of personalized diagnosis and treatment approaches in AD.
Why it matters
This multi-omics study of cerebrospinal fluid in older adults identified five major dimensions of heterogeneity associated with Alzheimer's disease and found overrepresentation of hemostasis, immune response and extracellular matrix signaling pathways. The work identifies molecular patterns and pathways that may relate to disease pathology, but it does not test any treatment or show a way to prevent or cure the disease.
Study details
- Evidence strengthModerate
How this study scored 50/100
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 | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2021 — within 6 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 | 5 / 7 | Cited 112 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 16.0 citations a year over 7 year(s) since 2021 |
| Impact for its field and year | 4 / 6 | Cited 11.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 3 / 4 | Cited 63 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Julius Popp: h-index 59 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Zurich: institution h-index 1,220 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 8 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 33794997) |
| Free to read | 2 / 2 | Free to read |
| Total | 50 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1186/s13195-021-00814-7
- PubMed: 33794997
- Original source →
- Free full text: Alzheimer s Research & Therapy →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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APA 7th
Clark, C., Dayon, L., Masoodi, M., Bowman, G. L., & Popp, J. (2021). An integrative multi-omics approach reveals new central nervous system pathway alterations in Alzheimer's disease. Alzheimer's research & therapy. https://doi.org/10.1186/s13195-021-00814-7
Vancouver
Clark C, Dayon L, Masoodi M, Bowman GL, Popp J. An integrative multi-omics approach reveals new central nervous system pathway alterations in Alzheimer's disease. Alzheimer's research & therapy. 2021. doi:10.1186/s13195-021-00814-7. PMID: 33794997.
BibTeX
@article{clark2021-33794997,
author = {Clark, C. and Dayon, L. and Masoodi, M. and Bowman, G. L. and Popp, J.},
title = {{An integrative multi-omics approach reveals new central nervous system pathway alterations in Alzheimer's disease}},
journal = {Alzheimer's research \& therapy},
year = {2021},
doi = {10.1186/s13195-021-00814-7},
pmid = {33794997},
url = {https://doi.org/10.1186/s13195-021-00814-7}
}
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