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The predominant form of the amyloid beta-protein precursor in human brain is protease nexin 2
Van Nostrand WE, Farrow JS, Wagner SL, Bhasin R, Goldgaber D, Cotman CW, Cunningham DD.. Proceedings of the National Academy of Sciences of the United States of America, 1991-11-01
Topic: Brain proteins, microglia and lab models
Plain-language summary
The amyloid beta protein and the amyloid beta-protein precursor (APP) are major constituents of senile plaques and cerebrovascular deposits in patients with Alzheimer disease and Down syndrome. Most human tissues contain mRNA that encodes forms of APP that contain the Kunitz protease inhibitor (KPI+) domain. A major 120-kDa protein corresponding to this KPI+ mRNA is also found in these tissues. This protein is identical to the protease inhibitor protease nexin 2. Brain contains an additional mRNA species that encodes a form of APP that lacks the KPI domain (KPI-). This latter mRNA has been suggested to encode a 105-kDa KPI- form of APP protein also found in brain. Using protease inhibitory functional assays, we show that both the 105-kDa and 120-kDa APP proteins in normal and Alzheimer disease brain contain the KPI domain. Moreover, KPI domain-specific precipitation assays reveal that KPI- forms of APP protein represent less than 14% of total brain APP. Lastly, an enriched fraction from total brain homogenate contains proteolytic activity that can process the purified 120-kDa KPI+ form of APP into a 105-kDa form, resulting in a high-molecular-mass doublet identical to that seen in brain. These findings indicate that although KPI- APP mRNA is abundant in brain, little corresponding protein is present. Thus, KPI+ APP protein (equivalent to protease nexin 2) is the predominant form of APP in human brain.
What this study adds
Evidence grade: Low
This study found that in normal and Alzheimer's disease brain, both the 105-kDa and 120-kDa amyloid precursor protein forms contain the Kunitz protease inhibitor domain, and that KPI- forms represent less than 14% of total brain APP. It is a basic biochemical finding about APP in brain tissue and does not test any treatment, cure or prevention.
Taken from this record’s own fields, not from reading the paper. The grade is assigned from the abstract’s wording; what that means.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Van Nostrand, W. E., Farrow, J. S., Wagner, S. L., Bhasin, R., Goldgaber, D., Cotman, C. W., et al. (1991). The predominant form of the amyloid beta-protein precursor in human brain is protease nexin 2. Proceedings of the National Academy of Sciences of the United States of America. https://doi.org/10.1073/pnas.88.22.10302
Vancouver
Van Nostrand WE, Farrow JS, Wagner SL, Bhasin R, Goldgaber D, Cotman CW, et al. The predominant form of the amyloid beta-protein precursor in human brain is protease nexin 2. Proceedings of the National Academy of Sciences of the United States of America. 1991. doi:10.1073/pnas.88.22.10302. PMID: 1946448.
BibTeX
@article{vannostrand1991-1946448,
author = {Van Nostrand, W. E. and Farrow, J. S. and Wagner, S. L. and Bhasin, R. and Goldgaber, D. and Cotman, C. W. and Cunningham, D. D.},
title = {{The predominant form of the amyloid beta-protein precursor in human brain is protease nexin 2}},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {1991},
doi = {10.1073/pnas.88.22.10302},
pmid = {1946448},
url = {https://doi.org/10.1073/pnas.88.22.10302}
}
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.
Key findings
- These findings indicate that although KPI- APP mRNA is abundant in brain, little corresponding protein is present.
Why it matters
This study found that in normal and Alzheimer's disease brain, both the 105-kDa and 120-kDa amyloid precursor protein forms contain the Kunitz protease inhibitor domain, and that KPI- forms represent less than 14% of total brain APP. It is a basic biochemical finding about APP in brain tissue and does not test any treatment, cure or prevention.
Study details
- Evidence strengthLow
How this study scored 39/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / 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 | 1991 — 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 | 4 / 7 | Cited 52 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.4 citations a year over 37 year(s) since 1991 |
| Impact for its field and year | 3 / 6 | Cited 4.5× 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 | 0 / 4 | Cited 0 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Dennis D. Cunningham: h-index 50 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of California, Irvine: institution h-index 1,195 (OpenAlex) |
| Multicenter collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 1946448) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 39 / 100 | — |
What each of these 20 components measures, and what this score is not →
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