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beta-amyloid peptides enhance alpha-synuclein accumulation and neuronal deficits in a transgenic mouse model linking Alzheimer's disease and Parkinson's disease
Masliah E, Rockenstein E, Veinbergs I, Sagara Y, Mallory M, Hashimoto M, Mucke L.. Proceedings of the National Academy of Sciences of the United States of America, 2001-09-25
Topic: Brain proteins, microglia and lab models
Alzheimer's disease and Parkinson's disease are associated with the cerebral accumulation of beta-amyloid and alpha-synuclein, respectively. Some patients have clinical and pathological features of both diseases, raising the possibility of overlapping pathogenetic pathways. We generated transgenic (tg) mice with neuronal expression of human beta-amyloid peptides, alpha-synuclein, or both. The functional and morphological alterations in doubly tg mice resembled the Lewy-body variant of Alzheimer's disease. These mice had severe deficits in learning and memory, developed motor deficits before alpha-synuclein singly tg mice, and showed prominent age-dependent degeneration of cholinergic neurons and presynaptic terminals. They also had more alpha-synuclein-immunoreactive neuronal inclusions than alpha-synuclein singly tg mice. Ultrastructurally, some of these inclusions were fibrillar in doubly tg mice, whereas all inclusions were amorphous in alpha-synuclein singly tg mice. beta-Amyloid peptides promoted aggregation of alpha-synuclein in a cell-free system and intraneuronal accumulation of alpha-synuclein in cell culture. beta-Amyloid peptides may contribute to the development of Lewy-body diseases by promoting the aggregation of alpha-synuclein and exacerbating alpha-synuclein-dependent neuronal pathologies. Therefore, treatments that block the production or accumulation of beta-amyloid peptides could benefit a broader spectrum of disorders than previously anticipated.
Key findings
- Alzheimer's disease and Parkinson's disease are associated with the cerebral accumulation of beta-amyloid and alpha-synuclein, respectively.
Why it matters
Mice expressing both human beta-amyloid and alpha-synuclein had worse learning, memory and motor deficits and more alpha-synuclein inclusions than mice with alpha-synuclein alone, and beta-amyloid promoted alpha-synuclein aggregation in cell-free and cell culture systems. This is animal and laboratory work suggesting beta-amyloid may worsen Lewy body disease, not a tested treatment.
Study details
- Evidence strengthLow
How this study scored 53/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Proceedings of the National Academy of Sciences of the United States of America) |
| Journal's citation record | 4 / 4 | Proceedings of the National Academy of Sciences: journal h-index 1,167 (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 | 1 / 5 | 2001 — older than 20 years, still counted |
| 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 | Laboratory or animal study (title names “transgenic”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 609 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 22.6 citations a year over 27 year(s) since 2001 |
| Impact for its field and year | 4 / 6 | Cited 14.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 36 other studies in this library |
| Still being cited | 3 / 4 | Cited 51 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Lennart Mucke: h-index 108 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of California, San Francisco: institution h-index 1,915 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 11572944) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 53 / 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. The record names 7 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Masliah, E., Rockenstein, E., Veinbergs, I., Sagara, Y., Mallory, M., Hashimoto, M., et al. (2001). beta-amyloid peptides enhance alpha-synuclein accumulation and neuronal deficits in a transgenic mouse model linking Alzheimer's disease and Parkinson's disease. Proceedings of the National Academy of Sciences of the United States of America. https://doi.org/10.1073/pnas.211412398
Vancouver
Masliah E, Rockenstein E, Veinbergs I, Sagara Y, Mallory M, Hashimoto M, et al. beta-amyloid peptides enhance alpha-synuclein accumulation and neuronal deficits in a transgenic mouse model linking Alzheimer's disease and Parkinson's disease. Proceedings of the National Academy of Sciences of the United States of America. 2001. doi:10.1073/pnas.211412398. PMID: 11572944.
BibTeX
@article{masliah2001-11572944,
author = {Masliah, E. and Rockenstein, E. and Veinbergs, I. and Sagara, Y. and Mallory, M. and Hashimoto, M. and Mucke, L.},
title = {{beta-amyloid peptides enhance alpha-synuclein accumulation and neuronal deficits in a transgenic mouse model linking Alzheimer's disease and Parkinson's disease}},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {2001},
doi = {10.1073/pnas.211412398},
pmid = {11572944},
url = {https://doi.org/10.1073/pnas.211412398}
}
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