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Intracellular APP processing and A beta production in Alzheimer disease
Wilson CA, Doms RW, Lee VM.. Journal of neuropathology and experimental neurology, 1999-08-01
Topic: Amyloid, tau and blood-test diagnosis
Senile plaques composed of A beta peptides are a histopathological hallmark of Alzheimer disease (AD). A role for A beta in the etiology of AD has been argued from analysis of mutations associated with a subset of early-onset familial AD (FAD). Expression of autosomal dominant mutations in the genes for the amyloid precursor protein (APP), presenilin 1 (PS1), and presenilin 2 (PS2) in affected patients, cultured cells, or transgenic mice leads to increased production of total A beta or increased production of A beta ending at residue 42 (A beta42).
Key findings
- A role for A beta in the etiology of AD has been argued from analysis of mutations associated with a subset of early-onset familial AD (FAD).
- Expression of autosomal dominant mutations in the genes for the amyloid precursor protein (APP), presenilin 1 (PS1), and presenilin 2 (PS2) in affected patients, cultured cells, or transgenic mice leads to increased production of total A beta or increased production of A beta ending at residue 42 (A beta42).
- Since A beta42 is the more amyloidogenic and toxic species in vitro and is the major component of amyloid senile plaques in vivo, overproduction of this peptide may play a crucial role in the pathogenesis of AD.
- Thus, an understanding of the production of A beta within the cell in normal and pathological conditions is critical to understanding early events in AD.
Why it matters
This review explains that mutations in APP, PS1 and PS2 in early-onset familial Alzheimer's disease increase production of total amyloid beta or of amyloid beta ending at residue 42. It is a summary of disease mechanisms and reports no treatment, cure or prevention.
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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 (Journal of neuropathology and experimental neurology) |
| Journal's citation record | 2 / 4 | Journal of Neuropathology & Experimental Neurology: journal h-index 239 (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 | 1999 — 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) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 187 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 6.4 citations a year over 29 year(s) since 1999 |
| Impact for its field and year | 4 / 6 | Cited 11.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 9 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 | 4 / 4 | Last-listed author Virginia M.‐Y. Lee: h-index 202 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Pennsylvania: institution h-index 1,859 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 10446803) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| 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
Wilson, C. A., Doms, R. W., & Lee, V. M. (1999). Intracellular APP processing and A beta production in Alzheimer disease. Journal of neuropathology and experimental neurology. https://doi.org/10.1097/00005072-199908000-00001
Vancouver
Wilson CA, Doms RW, Lee VM. Intracellular APP processing and A beta production in Alzheimer disease. Journal of neuropathology and experimental neurology. 1999. doi:10.1097/00005072-199908000-00001. PMID: 10446803.
BibTeX
@article{wilson1999-10446803,
author = {Wilson, C. A. and Doms, R. W. and Lee, V. M.},
title = {{Intracellular APP processing and A beta production in Alzheimer disease}},
journal = {Journal of neuropathology and experimental neurology},
year = {1999},
doi = {10.1097/00005072-199908000-00001},
pmid = {10446803},
url = {https://doi.org/10.1097/00005072-199908000-00001}
}
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