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Molecular Crossroads: Shared and Divergent Molecular Signatures in Alzheimer’s Disease and Dementia with Lewy Bodies
Sandesh Neupane, Tibor Hortobágyi. International Journal of Molecular Sciences, 2025-12-07
Topic: Brain proteins, microglia and lab models
Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) are the two most common forms of dementia due to neurodegeneration. AD is characterized by extracellular amyloid-β (Aβ) plaques and intracellular tau neurofibrillary tangles, whereas DLB is defined by α-synuclein (α-Syn)-containing Lewy bodies. Although AD and DLB exhibit divergent core features, the disorders frequently co-occur and converge on shared endpoints. Co-pathology is common and linked to more severe cognitive decline, faster progression, and clinicopathological heterogeneity. Here, we discuss the current understanding of shared and unique clinical and neuropathological features of AD and DLB. We compare genetic risk and pathological drivers (Aβ and tau in AD; α-Syn in DLB) and their overlapping co-pathology, and review downstream mechanisms-mitochondrial dysfunction, oxidative stress, neuroinflammation, and cerebrovascular contributions, including cerebral amyloid angiopathy. We highlight recent findings from state-of-the-art multi-omics (transcriptomic, proteomic, metabolomic, and single-cell/spatial studies) that reveal convergent and disease-specific molecular signatures of AD and DLB. We outline a framework for emerging next-generation biomarkers-from blood-based and cerebrospinal fluid assays to imaging and digital measures-for diagnosis and stratification, and discuss potential translational implications. Together, these advances help to disentangle shared from disease-specific mechanisms, which is essential for improved diagnosis and the development of precise, disease-modifying therapies.
Key findings
- Here, we discuss the current understanding of shared and unique clinical and neuropathological features of AD and DLB.
- We compare genetic risk and pathological drivers (Aβ and tau in AD; α-Syn in DLB) and their overlapping co-pathology, and review downstream mechanisms-mitochondrial dysfunction, oxidative stress, neuroinflammation, and cerebrovascular contributions, including cerebral amyloid angiopathy.
- We highlight recent findings from state-of-the-art multi-omics (transcriptomic, proteomic, metabolomic, and single-cell/spatial studies) that reveal convergent and disease-specific molecular signatures of AD and DLB.
- We outline a framework for emerging next-generation biomarkers-from blood-based and cerebrospinal fluid assays to imaging and digital measures-for diagnosis and stratification, and discuss potential translational implications.
- Together, these advances help to disentangle shared from disease-specific mechanisms, which is essential for improved diagnosis and the development of precise, disease-modifying therapies.
Why it matters
This review compares the molecular and pathological features of Alzheimer's disease and dementia with Lewy bodies and discusses emerging biomarkers. It is a discussion of shared and distinct biology, not a treatment or cure.
Study details
- Evidence strengthLow
How this study scored 41/100
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 (International Journal of Molecular Sciences) |
| Journal's citation record | 3 / 4 | International Journal of Molecular Sciences: journal h-index 426 (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 5 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.7 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 2 / 6 | Cited 2.7× 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 5 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Tibor Hortobágyi: h-index 60 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Zurich: institution h-index 1,220 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41465242) |
| Free to read | 2 / 2 | Free to read |
| Total | 41 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.3390/ijms262411811
- PubMed: 41465242
- Original source →
- Free full text: International Journal of Molecular Sciences →
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. Check the citation against the original before you use it.
APA 7th
Neupane, S., & Hortobágyi, T. (2025). Molecular Crossroads: Shared and Divergent Molecular Signatures in Alzheimer’s Disease and Dementia with Lewy Bodies. International Journal of Molecular Sciences. https://doi.org/10.3390/ijms262411811
Vancouver
Neupane S, Hortobágyi T. Molecular Crossroads: Shared and Divergent Molecular Signatures in Alzheimer’s Disease and Dementia with Lewy Bodies. International Journal of Molecular Sciences. 2025. doi:10.3390/ijms262411811. PMID: 41465242.
BibTeX
@article{neupane2025-41465242,
author = {Neupane, Sandesh and Hortobágyi, Tibor},
title = {{Molecular Crossroads: Shared and Divergent Molecular Signatures in Alzheimer’s Disease and Dementia with Lewy Bodies}},
journal = {International Journal of Molecular Sciences},
year = {2025},
doi = {10.3390/ijms262411811},
pmid = {41465242},
url = {https://doi.org/10.3390/ijms262411811}
}
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