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Home › Research › Down syndrome and Alzheimer's

Evidence that the rab5 effector APPL1 mediates APP-βCTF-induced dysfunction of endosomes in Down syndrome and Alzheimer's disease

Kim S, Sato Y, Mohan PS, Peterhoff C, Pensalfini A, Rigoglioso A, Jiang Y, Nixon RA.. Molecular psychiatry, 2015-07-21

This page is alzhub.org's plain-English summary of a published study, not the paper itself. It is generated from the record we hold for this study, sourced and linked below — check the original for the full text and methods.

✓ Peer-reviewed alzhub usefulness score 43 out of 100. Down syndrome and Alzheimer's

Topic: Disease mechanisms in lab and animal studies

β-Amyloid precursor protein (APP) and its cleaved products are strongly implicated in Alzheimer's disease (AD). Endosomes are highly active APP processing sites, and endosome anomalies associated with upregulated expression of early endosomal regulator, rab5, are the earliest known disease-specific neuronal response in AD. Here, we show that the rab5 effector APPL1 (adaptor protein containing pleckstrin homology domain, phosphotyrosine binding domain and leucine zipper motif) mediates rab5 overactivation in Down syndrome (DS) and AD, which is caused by elevated levels of the β-cleaved carboxy-terminal fragment of APP (βCTF). βCTF recruits APPL1 to rab5 endosomes, where it stabilizes active GTP-rab5, leading to pathologically accelerated endocytosis, endosome swelling and selectively impaired axonal transport of rab5 endosomes. In DS fibroblasts, APPL1 knockdown corrects these endosomal anomalies. βCTF levels are also elevated in AD brain, which is accompanied by abnormally high recruitment of APPL1 to rab5 endosomes as seen in DS fibroblasts. These studies indicate that persistent rab5 overactivation through βCTF-APPL1 interactions constitutes a novel APP-dependent pathogenic pathway in AD.

Key findings

Study details

How this study scored 43/100
How this study's score is builtJournal tier 9 of 10; Journal's citation record left out, no data; Study design 0 of 12; Strength of evidence 1 of 5; Peer-review validation 10 of 10; How recent 1 of 5; Sample size 0 of 4; Effect reported 0 of 3; Studied in people 0 of 3; Randomised / blinded 0 of 2; Times cited left out, no data; Citations per year left out, no data; Impact for its field and year left out, no data; Cited by studies here left out, no data; Still being cited left out, no data; Senior author's track record left out, no data; Institution's track record left out, no data; Multi-centre collaboration left out, no data; Indexed in PubMed 2 of 2; Free to read 2 of 2. 25 of the 58 points it could be judged on, which is 43 of 100. Total 43 of 100.25 of the 58 points we could judge = 43 of 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 25 of the 58 points we could judge it on, which is 43 out of 100.

ComponentPointsWhy
Journal tier 9 / 10 Tier 2 — leading specialty journal (Molecular psychiatry)
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 2016 — 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 26194181)
Free to read 2 / 2 Free to read
Points 25 / 58 Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 25 of the 58 points we could judge it on is 43 out of 100.
Total 43 / 100 —

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

Read the original

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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. The record names 8 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.

APA 7th

Kim, S., Sato, Y., Mohan, P. S., Peterhoff, C., Pensalfini, A., Rigoglioso, A., et al. (2016). Evidence that the rab5 effector APPL1 mediates APP-βCTF-induced dysfunction of endosomes in Down syndrome and Alzheimer's disease. Molecular psychiatry. https://doi.org/10.1038/mp.2015.97

Vancouver

Kim S, Sato Y, Mohan PS, Peterhoff C, Pensalfini A, Rigoglioso A, et al. Evidence that the rab5 effector APPL1 mediates APP-βCTF-induced dysfunction of endosomes in Down syndrome and Alzheimer's disease. Molecular psychiatry. 2016. doi:10.1038/mp.2015.97. PMID: 26194181.

BibTeX

@article{kim2016-26194181,
  author  = {Kim, S. and Sato, Y. and Mohan, P. S. and Peterhoff, C. and Pensalfini, A. and Rigoglioso, A. and Jiang, Y. and Nixon, R. A.},
  title   = {{Evidence that the rab5 effector APPL1 mediates APP-βCTF-induced dysfunction of endosomes in Down syndrome and Alzheimer's disease}},
  journal = {Molecular psychiatry},
  year    = {2016},
  doi     = {10.1038/mp.2015.97},
  pmid    = {26194181},
  url     = {https://doi.org/10.1038/mp.2015.97}
}

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