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40/100

✓ Peer-reviewed alzhub usefulness score 40 out of 100. Biomarkers

Topic: Disease mechanisms in lab and animal studies

Pathological amino-acid substitutions in the amyloid precursor protein (APP) and chemical γ-secretase modulators affect the processing of APP by the γ-secretase complex and the production of the amyloid-beta peptide Aβ42, the accumulation of which is considered causative of Alzheimer's disease. Here we demonstrate that mutations in the transmembrane domain of APP causing aggressive early-onset familial Alzheimer's disease affect both γ- and ε-cleavage sites, by raising the Aβ42/40 ratio and inhibiting the production of AICD50-99, one of the two physiological APP intracellular domains (ICDs). This is in sharp contrast to γ-secretase modulators, which shift Aβ42 production towards the shorter Aβ38, but unequivocally spare the ε-site and APP- and Notch-ICDs production. Molecular simulations suggest that familial Alzheimer's disease mutations modulate the flexibility of the APP transmembrane domain and the presentation of its γ-site, modifying at the same time, the solvation of the ε-site.

Key findings

Molecular simulations suggest that familial Alzheimer's disease mutations modulate the flexibility of the APP transmembrane domain and the presentation of its γ-site, modifying at the same time, the solvation of the ε-site.

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Study details

Evidence strengthLow

How this study scored 40/100

Published in a leading specialty 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 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 multi-centre collaboration, so those were left out: it earned 23 of the 58 points we could judge it on, which is 40 out of 100.

Component	Points	Why
Journal tier	9 / 10	Tier 2 — leading specialty journal (Nature communications)
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	2013 — 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	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
Multi-centre collaboration	— / 3	Institutions not listed — left out of this score
Indexed in PubMed	2 / 2	Indexed in PubMed (PMID 23907250)
Free to read	0 / 2	Behind a paywall — scores zero
Points	23 / 58	Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 23 of the 58 points we could judge it on is 40 out of 100.
Total	40 / 100	—

What each of these 20 components measures, and what this score is not →

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Cite this study APA, Vancouver, BibTeX · download .bib or .ris

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APA 7th

Dimitrov, M., Alattia, JR., Lemmin, T., Lehal, R., Fligier, A., Houacine, J., et al. (2013). Alzheimer's disease mutations in APP but not γ-secretase modulators affect epsilon-cleavage-dependent AICD production. Nature communications. https://doi.org/10.1038/ncomms3246

Vancouver

Dimitrov M, Alattia JR, Lemmin T, Lehal R, Fligier A, Houacine J, et al. Alzheimer's disease mutations in APP but not γ-secretase modulators affect epsilon-cleavage-dependent AICD production. Nature communications. 2013. doi:10.1038/ncomms3246. PMID: 23907250.

BibTeX

@article{dimitrov2013-23907250,
  author  = {Dimitrov, M. and Alattia, JR. and Lemmin, T. and Lehal, R. and Fligier, A. and Houacine, J. and Hussain, I. and Radtke, F. and others},
  title   = {{Alzheimer's disease mutations in APP but not γ-secretase modulators affect epsilon-cleavage-dependent AICD production}},
  journal = {Nature communications},
  year    = {2013},
  doi     = {10.1038/ncomms3246},
  pmid    = {23907250},
  url     = {https://doi.org/10.1038/ncomms3246}
}

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