Evidence map›Paper›PMID 21297258›Full record

ArticleJournal of Alzheimer's disease : JAD2011

A multi-center study of ACE and the risk of late-onset Alzheimer's disease.

Olivia Belbin, Kristelle Brown, Hui Shi, Christopher Medway, Richard Abraham, Peter Passmore, David Mann, A David Smith, Clive Holmes, Bernadette McGuinness and 12 more

Abstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of Alzheimer's disease : JAD, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 5 pooled it
2.3field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 5 syntheses or guidelines pooled it, 33 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Renin-angiotensin system gene expression and neurodegenerative diseases.Journal of the renin-angiotensin-aldosterone system : JRAAS · 2016
    Pooled it
  4. Pooled it
  5. Pooled it
  6. Trial
  7. New Genetic Associations Between Alzheimer's Disease and Its Key Risk Factors.Psychogeriatrics : the official journal of the Japanese Psychogeriatric Society · 2026
    Article
  8. Article
  9. Article
  10. Article
  11. Correlations betweenBioscience reports · 2017
    Article
  12. Article
  13. Article
  14. Association between ACE polymorphisms and osteoarthritis susceptibility.International journal of clinical and experimental pathology · 2015
    Article
  15. Article
  16. Review
  17. Article
  18. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors at 10 institutions in 3 countries.

Olivia BelbinDepartment of Clinical Chemistry, Institute of Genetics, Queen's Medical Centre, University of Nottingham, Nottingham, UK.
Kristelle Brown
Hui Shi
Christopher Medway
Richard Abraham
Peter Passmore
David Mann
A David Smith
Clive Holmes
Bernadette McGuinness
David Craig
Donald Warden
Reinhard Heun
Heike Kölsch
Seth Love
Noor Kalsheker
Julie Williams
Michael J Owen
Minerva Carrasquillo
Steven Younkin
Kevin Morgan
Patrick G Kehoe
University of Nottingham · GBCardiff University · GBQueen's University Belfast · GBFrenchay Hospital · GBMayo Clinic in Florida · USOptimat (United Kingdom) · GBQueen Elizabeth Hospital Birmingham · GBUniversity of Bonn · DEUniversity of Manchester · GBUniversity of Southampton · GB

Funding

National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD)U24AG021886 · NIA · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI TATIANA M. FOROUD · 2002 to 2026
$119.8M
Vascular Structure and Function in Cognitive AgingP01AG003949 · NIA · YESHIVA UNIVERSITY · PI Richard B. LIPTON · 1985 to 2026
$73.9M
SUPPLEMENT TO ALZHEIMERS DISEASE PATIENT REGISTRYU01AG006786 · NIA · MAYO CLINIC ROCHESTER · PI GRAFF-RADFORD, JONATHAN, JACK, CLIFFORD R. · 1986 to 2023
$49.6M
THE PGRN/TDP-43 AXIS IN ALZHEIMER?S DISEASE AND NEURODEGENERATIONP50AG016574 · NIA · MAYO CLINIC ROCHESTER · PI BU, GUOJUN · 1999 to 2018
$36.9M
TRANSGENIC MODELING OF TAUOPATHYP01AG017216 · NIA · MAYO CLINIC JACKSONVILLE · PI DICKSON, DENNIS WILLIAM · 1999 to 2011
$12.0M
PREDICTORS OF THE RATE OF COGNITIVE DECLINE IN ELDERLY SUBJECTSP50AG025711 · NIA · UNIVERSITY OF SOUTH FLORIDA · PI POTTER, HUNTINGTON · 2005 to 2010
$8.2M
PLASMA A BETA AS A SURROGATE GENETIC MARKER FOR LOADR01AG018023 · NIA · MAYO CLINIC JACKSONVILLE · PI YOUNKIN, STEVEN G · 2001 to 2012
$3.3M
Medical Research Council G0300429Medical Research Council G0902227NIA NIH HHS AG03949NIA NIH HHS AG17216NIA NIH HHS AG25711NIA NIH HHS P01 AG003949NIA NIH HHS P01 AG017216NIA NIH HHS P50 AG016574NIA NIH HHS P50 AG025711NIA NIH HHS P50 AG16574NIA NIH HHS R01 AG018023NIA NIH HHS R01 AG18023NIA NIH HHS U01 AG006786NIA NIH HHS U01 AG06576NIA NIH HHS U24 AG021886NIA NIH HHS U24AG21886
6 · The paper itself

Abstract

A key pathological feature of late-onset Alzheimer's disease (LOAD) is the abnormal extracellular accumulation of the amyloid-β (Aβ) peptide. Thus, altered Aβ degradation could be a major contributor to the development of LOAD. Variants in the gene encoding the Aβ-degrading enzyme, angiotensin-1 converting enzyme (ACE) therefore represent plausible candidates for association with LOAD pathology and risk. Following Alzgene meta-analyses of all published case-control studies, the ACE variants rs4291 and rs1800764 showed significant association with LOAD risk. Furthermore ACE haplotypes are associated with both plasma ACE levels and LOAD risk. We tested three ACE variants (rs4291, rs4343, and rs1800764) for association with LOAD in ten Caucasian case-control populations (n = 8,212). No association was found using multiple logistic models (all p > 0.09). We found no population heterogeneity (all p > 0.38) or evidence for association with LOAD risk following meta-analysis of the ten populations for rs4343 (OR = 1.00), rs4291 (OR = 0.97), or rs1800764 (OR = 0.99). Although we found no haplotypic association in our complete dataset (p = 0.51), a significant global haplotypic p-value was observed in one population (p = 0.007) due to an association of the H3 haplotype (OR = 0.72, p = 0.02) and a trend towards an association of H4 (OR = 1.38, p = 0.09) and H7 (OR = 2.07, p = 0.08) although these did not survive Bonferroni correction. Previously reported associations of ACE variants with LOAD will be diminished following this study. At best, ACE variants have modest effect sizes, which are likely part of a complex interaction between genetic, phenotypic and pharmacological effects that would be undetected in traditional case-control studies.

Indexed as

AgedAged, 80 and overAlzheimer DiseaseApolipoproteins ECase-Control StudiesEuropeFemaleGene FrequencyGenetic Predisposition to DiseaseGenotypeHumansLogistic ModelsMaleMeta-Analysis as TopicNorth AmericaOdds RatioApolipoproteins EPeptidyl-Dipeptidase A

Identifiers

PMID21297258
PMCPMC3655234
OpenAlexW1697077861

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.