Home › Research › Risk genes beyond APOE
Beta-secretase protein and activity are increased in the neocortex in Alzheimer disease
Fukumoto H, Cheung BS, Hyman BT, Irizarry MC.. Archives of neurology, 2002-09-01
Topic: Brain proteins, microglia and lab models
Context Amyloid plaques, a major pathological feature of Alzheimer disease (AD), are composed of an internal fragment of amyloid precursor protein (APP): the 4-kd amyloid-beta protein (Abeta). The metabolic processing of APP that results in Abeta formation requires 2 enzymatic cleavage events, a gamma-secretase cleavage dependent on presenilin, and a beta-secretase cleavage by the aspartyl protease beta-site APP-cleaving enzyme (BACE). Objective To test the hypothesis that BACE protein and activity are increased in regions of the brain that develop amyloid plaques in AD.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Fukumoto, H., Cheung, B. S., Hyman, B. T., & Irizarry, M. C. (2002). Beta-secretase protein and activity are increased in the neocortex in Alzheimer disease. Archives of neurology. https://doi.org/10.1001/archneur.59.9.1381
Vancouver
Fukumoto H, Cheung BS, Hyman BT, Irizarry MC. Beta-secretase protein and activity are increased in the neocortex in Alzheimer disease. Archives of neurology. 2002. doi:10.1001/archneur.59.9.1381. PMID: 12223024.
BibTeX
@article{fukumoto2002-12223024,
author = {Fukumoto, H. and Cheung, B. S. and Hyman, B. T. and Irizarry, M. C.},
title = {{Beta-secretase protein and activity are increased in the neocortex in Alzheimer disease}},
journal = {Archives of neurology},
year = {2002},
doi = {10.1001/archneur.59.9.1381},
pmid = {12223024},
url = {https://doi.org/10.1001/archneur.59.9.1381}
}
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.
Key findings
- The metabolic processing of APP that results in Abeta formation requires 2 enzymatic cleavage events, a gamma-secretase cleavage dependent on presenilin, and a beta-secretase cleavage by the aspartyl protease beta-site APP-cleaving enzyme (BACE).
- Objective To test the hypothesis that BACE protein and activity are increased in regions of the brain that develop amyloid plaques in AD.
- Methods We developed an antibody capture system to measure BACE protein level and BACE-specific beta-secretase activity in frontal, temporal, and cerebellar brain homogenates from 61 brains with AD and 33 control brains.
- Results In the brains with AD, BACE activity and protein were significantly increased (P Conclusions The BACE protein and activity levels are increased in brain regions affected by amyloid deposition and remain increased despite significant neuronal and synaptic loss in AD.
Why it matters
In brain tissue from 61 people with Alzheimer's disease and 33 people without it, the enzyme BACE (beta-secretase), which carries out one of the two cuts needed to make amyloid-beta, was found at higher levels and with higher activity. The authors report that BACE was raised "in brain regions affected by amyloid deposition" and stayed raised "despite significant neuronal and synaptic loss." This shows that BACE is altered in the Alzheimer's brain. It does not show that BACE causes the disease, and this study did not test any treatment.
New to this subject? Start with our plain-English guide: Genetics →
Study details
- Evidence strengthLow
How this study scored 47/100
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 (Archives of neurology) |
| Journal's citation record | 3 / 4 | Archives of Neurology: journal h-index 353 (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 | 2002 — 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 | 6 / 7 | Cited 702 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 27.0 citations a year over 26 year(s) since 2002 |
| Impact for its field and year | 4 / 6 | Cited 12.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 28 other studies in this library |
| Still being cited | 2 / 4 | Cited 38 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Hiroaki Fukumoto: h-index 26 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Massachusetts General Hospital: institution h-index 2,057 (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 12223024) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 47 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
May need a subscription OpenAlex found no free copy of the full text (checked 6 Feb 1020), so the publisher may charge for it. The PubMed abstract is free.
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here.
Later studies that cite this one
28 studies in the alzhub library list this one in their references. Showing the 8 highest-scoring.
Related studies in Risk genes beyond APOE
Also tagged “precursor”
1,339 studies in the library carry the topic tag “precursor”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 1,339 tagged studies.