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A hypothesis explaining Alzheimer's disease, Parkinson's disease, and dementia with Lewy bodies overlap
Victor Z. Lau, Ifeoluwa Oluleke Awogbindin, Dan Frenkel, Shawn Narain Whitehead, Marie‐Ève Tremblay. Alzheimer s & Dementia, 2025-06-01
Topic: Amyloid, tau and blood-test diagnosis
Lewy body-involving diseases (LBD) are commonly associated with Parkinson's disease (PD) featuring voluntary movement inhibition, due to dopaminergic neuron dysfunction in the substantia nigra. PD is clinically tracked through Lewy bodies (LB), composed of insoluble α-synuclein aggregates sequestered with organelles, particularly inside neurons. However, α-synuclein pathology also appears in incidental LBD, Parkinson's disease dementia, and dementia with LB (DLB). Incomplete explanations address how these clinical pathologies interrelate, LBD etiology variability, and frequently overlapping α-synuclein and Alzheimer's disease (AD) pathologies. We hypothesize that (1) chronic environmental insult exposure and (2) senescence(-like) neuron accumulation contribute toward initiating and sustaining LBD; individual cell vulnerability determines either cell reactivity, death, or senescence in response to environmental insults. We predicate that parkinsonian and other neurodegenerative symptoms over LBD progression involve (3) co-occurring AD pathologies, wherein dementia symptomology develops when synergistic glial senescence, tau hyperphosphorylation, and possible α-synuclein aggregation reach into regions involved in AD progression. HIGHLIGHTS: Senescence burden is predicted to explain α-synucleinopathy progression. Senescence and cell death are hypothesized to occur in α-synucleinopathies. Sub-apoptotic stress is proposed to induce senescence in α-synucleinopathies. Neuronal senescence likely first spreads α-synucleinopathies to new regions. Glial senescence likely underlies Parkinson's disease and Alzheimer's disease overlap.
Key findings
- Lewy body-involving diseases (LBD) are commonly associated with Parkinson's disease (PD) featuring voluntary movement inhibition, due to dopaminergic neuron dysfunction in the substantia nigra.
Why it matters
This hypothesis proposes that chronic environmental insult exposure and senescence-like neuron accumulation contribute toward initiating and sustaining Lewy body diseases, with co-occurring Alzheimer's disease pathologies involved in dementia symptomology. The hypothesis is presented as a proposed explanation, not a confirmed mechanism or treatment.
Study details
- Evidence strengthLow
How this study scored 43/100
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 & Dementia) |
| Journal's citation record | 2 / 4 | Alzheimer s & Dementia: journal h-index 228 (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 | 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 | 2 / 7 | Cited 14 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 4.7 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 3 / 6 | Cited 7.9× 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 | 1 / 4 | Cited 14 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Marie‐Ève Tremblay: h-index 67 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of British Columbia: institution h-index 1,424 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40528299) |
| Free to read | 2 / 2 | Free to read |
| Total | 43 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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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. Check the citation against the original before you use it.
APA 7th
Lau, V. Z., Awogbindin, I. O., Frenkel, D., Whitehead, S. N., & Tremblay, M. (2025). A hypothesis explaining Alzheimer's disease, Parkinson's disease, and dementia with Lewy bodies overlap. Alzheimer s & Dementia. https://doi.org/10.1002/alz.70363
Vancouver
Lau VZ, Awogbindin IO, Frenkel D, Whitehead SN, Tremblay M. A hypothesis explaining Alzheimer's disease, Parkinson's disease, and dementia with Lewy bodies overlap. Alzheimer s & Dementia. 2025. doi:10.1002/alz.70363. PMID: 40528299.
BibTeX
@article{lau2025-40528299,
author = {Lau, Victor Z. and Awogbindin, Ifeoluwa Oluleke and Frenkel, Dan and Whitehead, Shawn Narain and Tremblay, Marie‐Ève},
title = {{A hypothesis explaining Alzheimer's disease, Parkinson's disease, and dementia with Lewy bodies overlap}},
journal = {Alzheimer s \& Dementia},
year = {2025},
doi = {10.1002/alz.70363},
pmid = {40528299},
url = {https://doi.org/10.1002/alz.70363}
}
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