Home › Research › Lewy body dementia
Shared and disease-specific pathways in frontotemporal dementia and Alzheimer’s and Parkinson’s diseases
Muhammad Ali, Buddhiprabha Erabadda, Yike Chen, Ying Xu, Katherine Gong, Menghan Liu, Alexa Pichet Binette, Jigyasha Timsina et al.. Nature Medicine, 2025-07-15
Topic: Brain proteins, microglia and lab models
Abstract Neurodegenerative diseases (NDs), such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and frontotemporal dementia (FTD), exhibit distinct yet overlapping pathological mechanisms. Leveraging large-scale plasma proteomics data from the Global Neurodegeneration Proteomics Consortium, we analyzed 10,527 plasma samples (1,936 AD, 525 PD, 163 FTD, 1,638 dementia and 6,265 controls) to identify disease-specific and shared proteins across NDs. We identified 5,187 proteins significantly associated with AD, 3,748 with PD and 2,380 with FTD that revealed both common and divergent proteomic signatures, which were confirmed by multiple analytical approaches and orthogonal validation. PD and FTD showed the highest overlap ( r 2 = 0.44) and AD and PD the least ( r 2 = 0.04). Immune system, glycolysis, and matrisome-related pathways were enriched across all NDs, while disease-specific pathways included apoptotic processes in AD, endoplasmic reticulum–phagosome impairment in PD and platelet dysregulation in FTD. Network analysis identified key upstream regulators (RPS27A in AD, IRAK4 in PD and MAPK1 in FTD) potentially driving these proteomic changes. These findings reveal distinct and shared mechanisms across NDs, highlighting potential regulatory proteins and pathways for diagnostic and therapeutic strategies in neurodegeneration.
Key findings
- We identified 5,187 proteins significantly associated with AD, 3,748 with PD and 2,380 with FTD that revealed both common and divergent proteomic signatures, which were confirmed by multiple analytical approaches and orthogonal validation.
- These findings reveal distinct and shared mechanisms across NDs, highlighting potential regulatory proteins and pathways for diagnostic and therapeutic strategies in neurodegeneration.
Why it matters
This large plasma proteomics study identified proteins and pathways shared across and specific to Alzheimer's, Parkinson's and frontotemporal dementia, including potential regulatory proteins. These findings are about disease mechanisms and possible diagnostic or therapeutic targets, not about treating, curing or preventing Alzheimer's disease.
Study details
- Participants10,527
- Evidence strengthLow
How this study scored 63/100
Published in a top-tier journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 10 / 10 | Tier 1 — top-tier general journal (Nature Medicine) |
| Journal's citation record | 4 / 4 | Nature Medicine: journal h-index 763 (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 | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 4 / 4 | 10,527 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 4 / 7 | Cited 45 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 15.0 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 5 / 6 | Cited 28.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 2 other studies in this library |
| Still being cited | 2 / 4 | Cited 45 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Carlos C Cruchaga: h-index 102 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Oxford: institution h-index 2,205 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 8 institution(s) in 4 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40665052) |
| Free to read | 2 / 2 | Free to read |
| Total | 63 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1038/s41591-025-03833-1
- PubMed: 40665052
- Original source →
- Free full text: Nature Medicine →
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
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Ali, M., Erabadda, B., Chen, Y., Xu, Y., Gong, K., Liu, M., et al. (2025). Shared and disease-specific pathways in frontotemporal dementia and Alzheimer’s and Parkinson’s diseases. Nature Medicine. https://doi.org/10.1038/s41591-025-03833-1
Vancouver
Ali M, Erabadda B, Chen Y, Xu Y, Gong K, Liu M, et al. Shared and disease-specific pathways in frontotemporal dementia and Alzheimer’s and Parkinson’s diseases. Nature Medicine. 2025. doi:10.1038/s41591-025-03833-1. PMID: 40665052.
BibTeX
@article{ali2025-40665052,
author = {Ali, Muhammad and Erabadda, Buddhiprabha and Chen, Yike and Xu, Ying and Gong, Katherine and Liu, Menghan and Binette, Alexa Pichet and Timsina, Jigyasha and others},
title = {{Shared and disease-specific pathways in frontotemporal dementia and Alzheimer’s and Parkinson’s diseases}},
journal = {Nature Medicine},
year = {2025},
doi = {10.1038/s41591-025-03833-1},
pmid = {40665052},
url = {https://doi.org/10.1038/s41591-025-03833-1}
}
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here. Showing 12 of 18.
Later studies that cite this one
2 studies in the alzhub library list this one in their references.