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Trafficking and proteolytic processing of APP
Haass C, Kaether C, Thinakaran G, Sisodia S.. Cold Spring Harbor perspectives in medicine, 2012-05-01
Topic: Brain proteins, microglia and lab models
Accumulations of insoluble deposits of amyloid β-peptide are major pathological hallmarks of Alzheimer disease. Amyloid β-peptide is derived by sequential proteolytic processing from a large type I trans-membrane protein, the β-amyloid precursor protein. The proteolytic enzymes involved in its processing are named secretases. β- and γ-secretase liberate by sequential cleavage the neurotoxic amyloid β-peptide, whereas α-secretase prevents its generation by cleaving within the middle of the amyloid domain.
Key findings
- Amyloid β-peptide is derived by sequential proteolytic processing from a large type I trans-membrane protein, the β-amyloid precursor protein.
- The proteolytic enzymes involved in its processing are named secretases. β- and γ-secretase liberate by sequential cleavage the neurotoxic amyloid β-peptide, whereas α-secretase prevents its generation by cleaving within the middle of the amyloid domain.
- In this chapter we describe the cell biological and biochemical characteristics of the three secretase activities involved in the proteolytic processing of the precursor protein.
- In addition we outline how the precursor protein maturates and traffics through the secretory pathway to reach the subcellular locations where the individual secretases are preferentially active.
Why it matters
This chapter describes how amyloid-beta is produced from amyloid precursor protein by sequential cleavage by beta- and gamma-secretases, while alpha-secretase prevents its generation. It explains the basic biology of amyloid-beta production but does not report a treatment or cure.
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Study details
- Evidence strengthLow
How this study scored 52/100
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. We have no data on impact for its field and year, so that was left out: it earned 49 of the 94 points we could judge it on, which is 52 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Cold Spring Harbor perspectives in medicine) |
| Journal's citation record | 2 / 4 | Cold Spring Harbor Perspectives in Medicine: journal h-index 197 (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 | 2012 — within 20 year(s) of the newest study here |
| 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 | 7 / 7 | Cited 1,079 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 67.4 citations a year over 16 year(s) since 2012 |
| 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 | 3 / 6 | Cited by 25 other studies in this library |
| Still being cited | 3 / 4 | Cited 180 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Sangram S. Sisodia: h-index 101 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Chicago: institution h-index 1,769 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 22553493) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 49 / 94 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 49 of the 94 points we could judge it on is 52 out of 100. |
| Total | 52 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1101/cshperspect.a006270
- PubMed: 22553493
- Original source →
- Free full text: Cold Spring Harbor Perspectives in Medicine →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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
Haass, C., Kaether, C., Thinakaran, G., & Sisodia, S. (2012). Trafficking and proteolytic processing of APP. Cold Spring Harbor perspectives in medicine. https://doi.org/10.1101/cshperspect.a006270
Vancouver
Haass C, Kaether C, Thinakaran G, Sisodia S. Trafficking and proteolytic processing of APP. Cold Spring Harbor perspectives in medicine. 2012. doi:10.1101/cshperspect.a006270. PMID: 22553493.
BibTeX
@article{haass2012-22553493,
author = {Haass, C. and Kaether, C. and Thinakaran, G. and Sisodia, S.},
title = {{Trafficking and proteolytic processing of APP}},
journal = {Cold Spring Harbor perspectives in medicine},
year = {2012},
doi = {10.1101/cshperspect.a006270},
pmid = {22553493},
url = {https://doi.org/10.1101/cshperspect.a006270}
}
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