Evidence map›Paper›PMID 30689776›Full record

ArticleBrain : a journal of neurology2019

Polygenic hazard score, amyloid deposition and Alzheimer's neurodegeneration.

Chin Hong Tan, Luke W Bonham, Chun Chieh Fan, Elizabeth C Mormino, Leo P Sugrue, Iris J Broce, Christopher P Hess, Jennifer S Yokoyama, Gil D Rabinovici, Bruce L Miller and 15 more

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

Article in Brain : a journal of neurology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed, 2 pooled it
6.3field-weighted citation impact, top 3% 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

51 citing papers in PubMed, 2 syntheses or guidelines pooled it, 91 citations in OpenAlex.

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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

25 authors at 8 institutions in 3 countries.

Chin Hong TanDivision of Psychology, Nanyang Technological University, 48 Nanyang Avenue, Singapore.
Luke W BonhamDepartment of Neurology, University of California, San Francisco, 400 Parnassus Ave, San Francisco, CA, USA.
Chun Chieh FanDepartment of Cognitive Science, University of California, San Diego, 9500 Gilman Dr, La Jolla, CA, USA.
Elizabeth C MorminoDepartment of Neurology and Neurological Sciences, Stanford University, 300 Pasteur Dr, Palo Alto, CA, USA.
Leo P SugrueDepartment of Radiology and Biomedical Imaging, University of California, San Francisco, 500 Parnassus Avenue, San Francisco, CA, USA.
Iris J BroceDepartment of Radiology and Biomedical Imaging, University of California, San Francisco, 500 Parnassus Avenue, San Francisco, CA, USA.
Christopher P HessDepartment of Radiology and Biomedical Imaging, University of California, San Francisco, 500 Parnassus Avenue, San Francisco, CA, USA.
Jennifer S YokoyamaDepartment of Neurology, University of California, San Francisco, 400 Parnassus Ave, San Francisco, CA, USA.
Gil D RabinoviciDepartment of Neurology, University of California, San Francisco, 400 Parnassus Ave, San Francisco, CA, USA.
Bruce L MillerDepartment of Neurology, University of California, San Francisco, 400 Parnassus Ave, San Francisco, CA, USA.
Kristine YaffeDepartment of Neurology, University of California, San Francisco, 400 Parnassus Ave, San Francisco, CA, USA.
Gerard D SchellenbergDepartment of Pathology and Laboratory Medicine, University of Pennsylvania, 204 N Broad St, Philadelphia, PA, USA.
Karolina KauppiDepartment of Radiology, University of California, San Diego, 8929 University Center, La Jolla, CA, USA.
Dominic HollandDepartment of Neurosciences, University of California, San Diego, 9500 Gilman Dr, La Jolla, CA, USA.
Linda K McEvoyDepartment of Radiology, University of California, San Diego, 8929 University Center, La Jolla, CA, USA.
Walter A KukullNational Alzheimer's Coordinating Center, Department of Epidemiology, University of Washington, 1959 NE Pacific St, Seattle, WA, USA.
Duygu TosunDepartment of Radiology and Biomedical Imaging, University of California, San Francisco, 500 Parnassus Avenue, San Francisco, CA, USA.
Michael W WeinerDepartment of Radiology and Biomedical Imaging, University of California, San Francisco, 500 Parnassus Avenue, San Francisco, CA, USA.
Reisa A SperlingDepartment of Neurology, Massachusetts General Hospital, 15 Parkman St, Boston, MA, USA.
David A BennettRush Alzheimer's Disease Center, Rush University Medical Center, 1750 W Harrison St, Chicago, IL, USA.
Bradley T HymanDepartment of Neurology, Massachusetts General Hospital, 15 Parkman St, Boston, MA, USA.
Ole A AndreassenNORMENT Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Boks 1072 Blindern, Oslo, Norway.
Anders M DaleDepartment of Cognitive Science, University of California, San Diego, 9500 Gilman Dr, La Jolla, CA, USA.
Rahul S DesikanDepartment of Radiology and Biomedical Imaging, University of California, San Francisco, 500 Parnassus Avenue, San Francisco, CA, USA.
Alzheimer’s Disease Neuroimaging Initiative
University of California, San Francisco · USUniversity of California, San Diego · USMassachusetts General Hospital · USOslo University Hospital · NORush University Medical Center · USSeattle Pacific University · USStanford University · USUniversity of Pennsylvania · 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
SUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI SCHNEIDER, JULIE A. · 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
RISK FACTORS, PATHOLOGY, AND CLINICAL EXPRESSIONS OF ADR01AG015819 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1998 to 2024
$21.4M
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 AG049152NIA NIH HHS P30 AG010161NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG017917NIA NIH HHS U24 AG021886
6 · The paper itself

Abstract

Mounting evidence indicates that the polygenic basis of late-onset Alzheimer's disease can be harnessed to identify individuals at greatest risk for cognitive decline. We have previously developed and validated a polygenic hazard score comprising of 31 single nucleotide polymorphisms for predicting Alzheimer's disease dementia age of onset. In this study, we examined whether polygenic hazard scores are associated with: (i) regional tracer uptake using amyloid PET; (ii) regional volume loss using longitudinal MRI; (iii) post-mortem regional amyloid-β protein and tau associated neurofibrillary tangles; and (iv) four common non-Alzheimer's pathologies. Even after accounting for APOE, we found a strong association between polygenic hazard scores and amyloid PET standard uptake volume ratio with the largest effects within frontal cortical regions in 980 older individuals across the disease spectrum, and longitudinal MRI volume loss within the entorhinal cortex in 607 older individuals across the disease spectrum. We also found that higher polygenic hazard scores were associated with greater rates of cognitive and clinical decline in 632 non-demented older individuals, even after controlling for APOE status, frontal amyloid PET and entorhinal cortex volume. In addition, the combined model that included polygenic hazard scores, frontal amyloid PET and entorhinal cortex volume resulted in a better fit compared to a model with only imaging markers. Neuropathologically, we found that polygenic hazard scores were associated with regional post-mortem amyloid load and neuronal neurofibrillary tangles, even after accounting for APOE, validating our imaging findings. Lastly, polygenic hazard scores were associated with Lewy body and cerebrovascular pathology. Beyond APOE, we show that in living subjects, polygenic hazard scores were associated with amyloid deposition and neurodegeneration in susceptible brain regions. Polygenic hazard scores may also be useful for the identification of individuals at the highest risk for developing multi-aetiological dementia.

Indexed as

AgedAged, 80 and overAlzheimer DiseaseFemaleHumansMaleMultifactorial InheritanceNeurodegenerative DiseasesPlaque, Amyloid

Identifiers

PMID30689776
PMCPMC6351776
OpenAlexW2914712649

What OpenQuestion holds

Textmetadata
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.