Home › Research › Down syndrome and Alzheimer's
Age- and region-dependent alterations in Abeta-degrading enzymes: implications for Abeta-induced disorders
Caccamo A, Oddo S, Sugarman MC, Akbari Y, LaFerla FM.. Neurobiology of aging, 2005-05-01
Topic: Disease mechanisms in lab and animal studies
Accumulation of amyloid beta-protein (Abeta) is a fundamental feature of certain human brain disorders such as Alzheimer's disease (AD) and Down syndrome and also of the skeletal muscle disorder inclusion body myositis (IBM). Emerging evidence suggests that the steady-state levels of Abeta are determined by the balance between production and degradation. Although the proteolytic processes leading to Abeta formation have been extensively studied, less is known about the proteases that degrade Abeta, which include insulin-degrading enzyme (IDE) and neprilysin (NEP). Here we measured the steady-state levels of these proteases as a function of age and brain/muscle region in mice and humans. In the hippocampus, which is vulnerable to AD pathology, IDE and NEP steady-state levels diminish as function of age. By contrast, in the cerebellum, a brain region not marked by significant Abeta accumulation, NEP and IDE levels either increase or remain unaltered during aging. Moreover, the steady-state levels of IDE and NEP are significantly higher in the cerebellum compared to the cortex and hippocampus. We further show that IDE is more oxidized in the hippocampus compared to the cerebellum of AD patients. In muscle, we find differential levels of IDE and NEP in fast versus slow twitch muscle fibers that varies with aging. These findings suggest that age- and region-specific changes in the proteolytic clearance of Abeta represent a critical pathogenic mechanism that may account for the susceptibility of particular brain or muscle regions in AD and IBM.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Caccamo, A., Oddo, S., Sugarman, M. C., Akbari, Y., & LaFerla, F. M. (2005). Age- and region-dependent alterations in Abeta-degrading enzymes: implications for Abeta-induced disorders. Neurobiology of aging. https://doi.org/10.1016/j.neurobiolaging.2004.06.013
Vancouver
Caccamo A, Oddo S, Sugarman MC, Akbari Y, LaFerla FM. Age- and region-dependent alterations in Abeta-degrading enzymes: implications for Abeta-induced disorders. Neurobiology of aging. 2005. doi:10.1016/j.neurobiolaging.2004.06.013. PMID: 15708439.
BibTeX
@article{caccamo2005-15708439,
author = {Caccamo, A. and Oddo, S. and Sugarman, M. C. and Akbari, Y. and LaFerla, F. M.},
title = {{Age- and region-dependent alterations in Abeta-degrading enzymes: implications for Abeta-induced disorders}},
journal = {Neurobiology of aging},
year = {2005},
doi = {10.1016/j.neurobiolaging.2004.06.013},
pmid = {15708439},
url = {https://doi.org/10.1016/j.neurobiolaging.2004.06.013}
}
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
- Emerging evidence suggests that the steady-state levels of Abeta are determined by the balance between production and degradation.
- By contrast, in the cerebellum, a brain region not marked by significant Abeta accumulation, NEP and IDE levels either increase or remain unaltered during aging.
- Moreover, the steady-state levels of IDE and NEP are significantly higher in the cerebellum compared to the cortex and hippocampus.
- We further show that IDE is more oxidized in the hippocampus compared to the cerebellum of AD patients.
- In muscle, we find differential levels of IDE and NEP in fast versus slow twitch muscle fibers that varies with aging.
Study details
- Evidence strengthLow
How this study scored 36/100
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. 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 21 of the 58 points we could judge it on, which is 36 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Neurobiology of aging) |
| 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 | 2005 — 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 15708439) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 21 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 21 of the 58 points we could judge it on is 36 out of 100. |
| Total | 36 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Free copy unknown: no free-copy check has an answer for this record yet. That does not mean it is paywalled.
Related
Studies in the library that share something with this one. The line above each title says what.
Related studies in Down syndrome and Alzheimer's
Also tagged “presenilin”
344 studies in the library carry the topic tag “presenilin”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 344 tagged studies.