Evidence map›Paper›PMID 29177679›Full record

ArticleActa neuropathologica2018

Polygenic hazard score: an enrichment marker for Alzheimer's associated amyloid and tau deposition.

Chin Hong Tan, Chun Chieh Fan, Elizabeth C Mormino, Leo P Sugrue, Iris J Broce, Christopher P Hess, William P Dillon, Luke W Bonham, Jennifer S Yokoyama, Celeste M Karch and 14 more

Open access · bronzeAbstract readEvaluation Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Acta neuropathologica, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed, 5 pooled it
7.3field-weighted citation impact, top 2% 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

63 citing papers in PubMed, 5 syntheses or guidelines pooled it, 103 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Polygenic risk and hazard scores for Alzheimer's disease prediction.Annals of clinical and translational neurology · 2019
    Pooled it
  5. Pooled it
  6. Article
  7. Polygenic risk scores in neurological disorders: restless legs syndrome as a translational model.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2026
    Article
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  15. Correlations between Dementia and Loneliness.International journal of molecular sciences · 2023
    Review
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  17. Article
  18. Article
  19. Article
  20. Review

3 more citing papers are in PubMed but not listed here.

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

24 authors at 5 institutions in 2 countries.

Chin Hong TanNeuroradiology Section, Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, USA. chinhong.tan@ucsf.edu.
Chun Chieh FanDepartment of Cognitive Science, University of California, La Jolla, San Diego, CA, USA.
Elizabeth C MorminoDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA.
Leo P SugrueNeuroradiology Section, Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, USA.
Iris J BroceNeuroradiology Section, Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, USA.
Christopher P HessNeuroradiology Section, Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, USA.
William P DillonNeuroradiology Section, Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, USA.
Luke W BonhamDepartment of Neurology, University of California, San Francisco, San Francisco, CA, USA.
Jennifer S YokoyamaDepartment of Neurology, University of California, San Francisco, San Francisco, CA, USA.
Celeste M KarchDepartment of Psychiatry, Washington University in St. Louis, St. Louis, MO, USA.
James B BrewerDepartment of Neurosciences, University of California, La Jolla, San Diego, CA, USA.
Gil D RabinoviciDepartment of Neurology, University of California, San Francisco, San Francisco, CA, USA.
Bruce L MillerDepartment of Neurology, University of California, San Francisco, San Francisco, CA, USA.
Gerard D SchellenbergDepartment of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Karolina KauppiDepartment of Radiology, University of California, La Jolla, San Diego, CA, USA.
Howard A FeldmanDepartment of Neurosciences, University of California, La Jolla, San Diego, CA, USA.
Dominic HollandDepartment of Neurosciences, University of California, La Jolla, San Diego, CA, USA.
Linda K McEvoyDepartment of Radiology, University of California, La Jolla, San Diego, CA, USA.
Bradley T HymanDepartment of Neurology, Massachusetts General Hospital, Boston, MA, USA.
David A BennettRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
Ole A AndreassenNORMENT Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Anders M DaleDepartment of Cognitive Science, University of California, La Jolla, San Diego, CA, USA.
Rahul S DesikanNeuroradiology Section, Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, USA. rahul.desikan@ucsf.edu.ORCID 0000-0002-4151-6017
Alzheimer’s Disease Neuroimaging Initiative
University of California, San Francisco · USUniversity of California San Diego · USRush University Medical Center · USOslo University Hospital · NOWashington University in St. Louis · US

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
Alzheimer's Disease Genetics ConsortiumU01AG032984 · NIA · UNIVERSITY OF PENNSYLVANIA · PI SCHELLENBERG, GERARD DAVID · 2009 to 2024
$60.4M
VIRUS-INDUCED BRAIN PATHOLOGYP50AG005131 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BREWER, JAMES B · 1985 to 2018
$55.4M
SUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BARNES, LISA L · 1991 to 2020
$49.1M
EPIDEMIOLOGY OF NEURAL RESERVE AND NEUROBIOLOGY IN AGINGR01AG017917 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 2001 to 2023
$43.3M
UCSD Shiley-Marcos Alzheimer's Disease Research Center P30P30AG062429 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Steven Dyal Edland · 2019 to 2026
$34.9M
PrPSc SPECIFIC INTERACTION WITH NOVEL PrP-Fc FUSION PROTEINSP50AG023501 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MILLER, BRUCE L · 2004 to 2018
$27.1M
RISK FACTORS, PATHOLOGY, AND CLINICAL EXPRESSIONS OF ADR01AG015819 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1998 to 2024
$21.4M
Risk Factors, Pathology, and Clinical Expressions of ADRF1AG015819 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 2014 to 2014
$6.0M
Early Age-of-Onset AD: Clinical Heterogeneity and Network DegenerationR01AG045611 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI RABINOVICI, GIL DAN · 2014 to 2018
$3.1M
Modeling the Aging EpigenomeDP1OD006849 · OD · HARVARD MEDICAL SCHOOL · PI YANKNER, BRUCE A · 2010 to 2011
$1.7M
RNA signatures of frontotemporal dementia and ALS due to C9ORF72 expansionK01AG049152 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI YOKOYAMA, JENNIFER S · 2015 to 2019
$648k
NIA NIH HHS K01 AG046374NIA NIH HHS K01 AG049152NIA NIH HHS K01 AG051718NIA NIH HHS P30 AG010161NIA NIH HHS P30 AG062429NIA NIH HHS P50 AG005131NIA NIH HHS P50 AG023501NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG017917NIA NIH HHS R01 AG045611NIA NIH HHS RF1 AG015819NIA NIH HHS U01 AG032984NIA NIH HHS U24 AG021886NIH HHS AG046374NIH HHS DP1 OD006849NIH HHS K01AG049152NIH HHS P20AG10161NIH HHS R01AG15819NIH HHS R01AG17917
6 · The paper itself

Abstract

There is an urgent need for identifying nondemented individuals at the highest risk of progressing to Alzheimer's disease (AD) dementia. Here, we evaluated whether a recently validated polygenic hazard score (PHS) can be integrated with known in vivo cerebrospinal fluid (CSF) or positron emission tomography (PET) biomarkers of amyloid, and CSF tau pathology to prospectively predict cognitive and clinical decline in 347 cognitive normal (CN; baseline age range = 59.7-90.1, 98.85% white) and 599 mild cognitively impaired (MCI; baseline age range = 54.4-91.4, 98.83% white) individuals from the Alzheimer's Disease Neuroimaging Initiative 1, GO, and 2. We further investigated the association of PHS with post-mortem amyloid load and neurofibrillary tangles in the Religious Orders Study and Memory and Aging Project (ROSMAP) cohort (N = 485, age at death range = 71.3-108.3). In CN and MCI individuals, we found that amyloid and total tau positivity systematically varies as a function of PHS. For individuals in greater than the 50th percentile PHS, the positive predictive value for amyloid approached 100%; for individuals in less than the 25th percentile PHS, the negative predictive value for total tau approached 85%. High PHS individuals with amyloid and tau pathology showed the steepest longitudinal cognitive and clinical decline, even among APOE ε4 noncarriers. Among the CN subgroup, we similarly found that PHS was strongly associated with amyloid positivity and the combination of PHS and biomarker status significantly predicted longitudinal clinical progression. In the ROSMAP cohort, higher PHS was associated with higher post-mortem amyloid load and neurofibrillary tangles, even in APOE ε4 noncarriers. Together, our results show that even after accounting for APOE ε4 effects, PHS may be useful in MCI and preclinical AD therapeutic trials to enrich for biomarker-positive individuals at highest risk for short-term clinical progression.

Indexed as

AgedAged, 80 and overAlzheimer DiseaseAmyloidApolipoproteins EBiomarkersBrainCognitive DysfunctionCohort StudiesFemaleHumansMaleMiddle AgedMultifactorial InheritanceNeurofibrillary TanglesPositron-Emission TomographyAmyloidApolipoproteins EBiomarkersMAPT protein, humantau ProteinsAlzheimer’s diseaseAmyloidPolygenic riskTau

Identifiers

PMID29177679
PMCPMC5758038
OpenAlexW2951267899

What OpenQuestion holds

Textmetadata
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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.