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Cytosolic beta-amyloid deposition and supranuclear cataracts in lenses from people with Alzheimer's disease
Goldstein LE, Muffat JA, Cherny RA, Moir RD, Ericsson MH, Huang X, Mavros C, Coccia JA et al.. Lancet (London, England), 2003-04-01
Topic: Amyloid, tau and blood-test diagnosis
Background Pathological hallmarks of Alzheimer's disease include cerebral beta-amyloid (Abeta) deposition, amyloid accumulation, and neuritic plaque formation. We aimed to investigate the hypothesis that molecular pathological findings associated with Alzheimer's disease overlap in the lens and brain. Methods We obtained postmortem specimens of eyes and brain from nine individuals with Alzheimer's disease and eight controls without the disorder, and samples of primary aqueous humour from three people without the disorder who were undergoing cataract surgery. Dissected lenses were analysed by slit-lamp stereophotomicroscopy, western blot, tryptic-digest/mass spectrometry electrospray ionisation, and anti-Abeta surface-enhanced laser desorption ionisation (SELDI) mass spectrometry, immunohistochemistry, and immunogold electron microscopy. Aqueous humour was analysed by anti-Abeta SELDI mass spectrometry. We did binding and aggregation studies to investigate Abeta-lens protein interactions. Findings We identified Abeta1-40 and Abeta1-42 in lenses from people with and without Alzheimer's disease at concentrations comparable with brain, and Abeta1-40 in primary aqueous humour at concentrations comparable with cerebrospinal fluid. Abeta accumulated in lenses from individuals with Alzheimer's disease as electron-dense deposits located exclusively in the cytoplasm of supranuclear/deep cortical lens fibre cells (n=4). We consistently saw equatorial supranuclear cataracts in lenses from people with Alzheimer's disease (n=9) but not in controls (n=8). These supranuclear cataracts colocalised with enhanced Abeta immunoreactivity and birefringent Congo Red staining. Synthetic Abeta bound alphaB-crystallin, an abundant cytosolic lens protein. Abeta promoted lens protein aggregation that showed protofibrils, birefringent Congo Red staining, and Abeta/alphaB-crystallin coimmunoreactivity. Interpretation Abeta is present in the cytosol of lens fibre cells of people with Alzheimer's disease. Lens Abeta might promote regionally-specific lens protein aggregation, extracerebral amyloid formation, and supranuclear cataracts.
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APA 7th
Goldstein, L. E., Muffat, J. A., Cherny, R. A., Moir, R. D., Ericsson, M. H., Huang, X., et al. (2003). Cytosolic beta-amyloid deposition and supranuclear cataracts in lenses from people with Alzheimer's disease. Lancet (London, England). https://doi.org/10.1016/s0140-6736(03)12981-9
Vancouver
Goldstein LE, Muffat JA, Cherny RA, Moir RD, Ericsson MH, Huang X, et al. Cytosolic beta-amyloid deposition and supranuclear cataracts in lenses from people with Alzheimer's disease. Lancet (London, England). 2003. doi:10.1016/s0140-6736(03)12981-9. PMID: 12699953.
BibTeX
@article{goldstein2003-12699953,
author = {Goldstein, L. E. and Muffat, J. A. and Cherny, R. A. and Moir, R. D. and Ericsson, M. H. and Huang, X. and Mavros, C. and Coccia, J. A. and others},
title = {{Cytosolic beta-amyloid deposition and supranuclear cataracts in lenses from people with Alzheimer's disease}},
journal = {Lancet (London, England)},
year = {2003},
doi = {10.1016/s0140-6736(03)12981-9},
pmid = {12699953},
url = {https://doi.org/10.1016/s0140-6736(03)12981-9}
}
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Key findings
- We aimed to investigate the hypothesis that molecular pathological findings associated with Alzheimer's disease overlap in the lens and brain.
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Study details
- Evidence strengthLow
How this study scored 41/100
Published in a top-tier journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multicenter collaboration, so those were left out: it earned 24 of the 58 points we could judge it on, which is 41 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 10 / 10 | Tier 1 — top-tier general journal (Lancet (London, England)) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | 2003 — 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 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 12699953) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 24 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 24 of the 58 points we could judge it on is 41 out of 100. |
| Total | 41 / 100 | — |
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