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.

43/100

✓ Peer-reviewed alzhub usefulness score 43 out of 100. Genetics

Topic: Genetics and APOE

Plain-language summary

Common variants of about 20 genes contributing to AD risk have so far been identified through genome-wide association studies (GWAS). However, there is still a large proportion of heritability that might be explained by rare but functionally important variants. One of the so far identified genes with rare AD causing variants is ADAM10. Using whole-genome sequencing we now identified a single rare nonsynonymous variant (SNV) rs142946965 [p.R215I] in ADAM17 co-segregating with an autosomal-dominant pattern of late-onset AD in one family. Subsequent genotyping and analysis of available whole-exome sequencing data of additional case/control samples from Germany, UK, and USA identified five variant carriers among AD patients only. The mutation inhibits pro-protein cleavage and the formation of the active enzyme, thus leading to loss-of-function of ADAM17 alpha-secretase. Further, we identified a strong negative correlation between ADAM17 and APP gene expression in human brain and present in vitro evidence that ADAM17 negatively controls the expression of APP. As a consequence, p.R215I mutation of ADAM17 leads to elevated Aß formation in vitro. Together our data supports a causative association of the identified ADAM17 variant in the pathogenesis of AD.

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

APA 7th

Hartl, D., May, P., Gu, W., Mayhaus, M., Pichler, S., Spaniol, C., et al. (2020). A rare loss-of-function variant of ADAM17 is associated with late-onset familial Alzheimer disease. Molecular psychiatry. https://doi.org/10.1038/s41380-018-0091-8

Vancouver

Hartl D, May P, Gu W, Mayhaus M, Pichler S, Spaniol C, et al. A rare loss-of-function variant of ADAM17 is associated with late-onset familial Alzheimer disease. Molecular psychiatry. 2020. doi:10.1038/s41380-018-0091-8. PMID: 29988083.

BibTeX

@article{hartl2020-29988083,
  author  = {Hartl, Daniela and May, Patrick and Gu, Wei and Mayhaus, Manuel and Pichler, Sabrina and Spaniol, Christian and Glaab, Enrico and Bobbili, Dheeraj Reddy and others},
  title   = {{A rare loss-of-function variant of ADAM17 is associated with late-onset familial Alzheimer disease}},
  journal = {Molecular psychiatry},
  year    = {2020},
  doi     = {10.1038/s41380-018-0091-8},
  pmid    = {29988083},
  url     = {https://doi.org/10.1038/s41380-018-0091-8}
}

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's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.

How to read this study

Design: our record does not state a study design, so check the methods section of the original before weighing the result.
Size: the record gives no participant count. Look for one in the original before trusting a pattern.
Effect: the record gives no effect size, so the summary above cannot say how large any difference was.

What the evidence grade means here

This page is graded low. alzhub.org assigns the grade automatically from keywords in the abstract, not from reading the paper. Low means the abstract matched neither pattern. It is the default label, and it does not mean the work is poor; many sound lab and imaging papers land here. It can add at most 5 of the 100 points in the study score, and it is a label about design, not a verdict on whether the findings are true.

New to reading papers? Six questions to ask of any Alzheimer’s study · how we score.

Key findings

Subsequent genotyping and analysis of available whole-exome sequencing data of additional case/control samples from Germany, UK, and USA identified five variant carriers among AD patients only.
The mutation inhibits pro-protein cleavage and the formation of the active enzyme, thus leading to loss-of-function of ADAM17 alpha-secretase.
Further, we identified a strong negative correlation between ADAM17 and APP gene expression in human brain and present in vitro evidence that ADAM17 negatively controls the expression of APP.
As a consequence, p.R215I mutation of ADAM17 leads to elevated Aß formation in vitro.
Together our data supports a causative association of the identified ADAM17 variant in the pathogenesis of AD.

New to this subject? Start with our plain-English guide: Genetics →

Study details

Evidence strengthLow

How this study scored 43/100

Published in a leading specialty 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, multicenter collaboration and free to read, so those were left out: it earned 24 of the 56 points we could judge it on, which is 43 out of 100.

Component	Points	Why
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	2 / 5	2020 — within 10 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)
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 29988083)
Free to read	— / 2	Access not recorded — left out of this score
Points	24 / 56	Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 24 of the 56 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

Free copy unknown: no free-copy check has an answer for this record yet. That does not mean it is paywalled.

Studies in the library that share something with this one. The line above each title says what.

Related studies in Genetics from nearby years

Also tagged “genetics”

346 studies in the library carry the topic tag “genetics”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 346 tagged studies.

Studies sharing this one's topic tags

Similar studies

More on Genetics

See all studies in Genetics →