Evidence map›Paper›PMID 24166411›Full record

ArticleMolecular psychiatry2014

The SORL1 gene and convergent neural risk for Alzheimer's disease across the human lifespan.

D Felsky, P Szeszko, L Yu, W G Honer, P L De Jager, J A Schneider, A K Malhotra, T Lencz, T Ikuta, J Pipitone and 7 more

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

Article in Molecular psychiatry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed, 1 pooled it
4.5field-weighted citation impact, top 6% 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

26 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.

  1. Pooled it
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  10. [Verification of a sporadic Alzheimer disease model in SORL1 gene knockout mice].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2018
    Article
  11. Religious Orders Study and Rush Memory and Aging Project.Journal of Alzheimer's disease : JAD · 2018
    Review
  12. Article
  13. Genetic epistasis regulates amyloid deposition in resilient aging.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2017
    Article
  14. Review
  15. Article
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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

17 authors at 6 institutions in 2 countries.

D Felsky1] Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, ON, Canada [2] Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
P Szeszko1] Division of Psychiatry Research, Zucker Hillside Hospital, North Shore-LIJ Health System, Glen Oaks, NY, USA [2] Center for Psychiatric Neuroscience, The Feinstein Institute for Medical Research, Manhasset, NY, USA [3] Departments of Psychiatry and Molecular Medicine, Hofstra North Shore-LIJ School of Medicine, Hempstead, NY, USA.
L Yu1] Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA [2] Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
W G HonerBC Mental Health and Addictions Research Institute, University of British Columbia, Vancouver, BC, Canada.
P L De Jager1] Program in Translational NeuroPsychiatric Genomics, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA [2] Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.
J A SchneiderRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
A K Malhotra1] Division of Psychiatry Research, Zucker Hillside Hospital, North Shore-LIJ Health System, Glen Oaks, NY, USA [2] Center for Psychiatric Neuroscience, The Feinstein Institute for Medical Research, Manhasset, NY, USA [3] Departments of Psychiatry and Molecular Medicine, Hofstra North Shore-LIJ School of Medicine, Hempstead, NY, USA.
T Lencz1] Division of Psychiatry Research, Zucker Hillside Hospital, North Shore-LIJ Health System, Glen Oaks, NY, USA [2] Center for Psychiatric Neuroscience, The Feinstein Institute for Medical Research, Manhasset, NY, USA [3] Departments of Psychiatry and Molecular Medicine, Hofstra North Shore-LIJ School of Medicine, Hempstead, NY, USA.
T IkutaDepartment of Communication Sciences and Disorders, School of Applied Science, University of Mississippi, Oxford, MS, USA.
J PipitoneCentre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
M M Chakravarty1] Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, ON, Canada [2] Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada.
N J LobaughCentre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
B H Mulsant1] Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, ON, Canada [2] Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
B G Pollock1] Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, ON, Canada [2] Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
J L Kennedy1] Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, ON, Canada [2] Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
D A Bennett1] Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA [2] Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
A N Voineskos1] Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, ON, Canada [2] Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
University of Toronto · CANorthwell Health · USRush University Medical Center · USBC Mental Health & Substance Use Services · CAHarvard University · USUniversity of Mississippi · US

Funding

SUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 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
Striatal D2/D3 Dopamine receptor availability in first episode schizophreniaP50MH080173 · NIMH · FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH · PI GREGERSEN, PETER K. · 2008 to 2012
$10.4M
Genetic Epidemiology of Cognitive Decline in an Aging Population SampleR01AG030146 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI EVANS, DENIS A · 2007 to 2018
$6.2M
Effects of Maintenance Treatment with Olanzapine vs. Placebo on Brain StructureR01MH099167 · NIMH · CENTRE FOR ADDICTION AND MENTAL HEALTH · PI VOINESKOS, ARISTOTLE NICHOLAS · 2013 to 2017
$1.4M
CIHRNIA NIH HHS P30 AG010161NIA NIH HHS P30AG10161NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG017917NIA NIH HHS R01 AG030146NIA NIH HHS R01AG15819NIA NIH HHS R01AG17917NIA NIH HHS R01AG30146NIMH NIH HHS P50 MH080173NIMH NIH HHS P50MH080173NIMH NIH HHS R01 MH099167NIMH NIH HHS R01MH099167
6 · The paper itself

Abstract

Prior to intervention trials in individuals genetically at-risk for late-onset Alzheimer's disease, critical first steps are identifying where (neuroanatomic effects), when (timepoint in the lifespan) and how (gene expression and neuropathology) Alzheimer's risk genes impact the brain. We hypothesized that variants in the sortilin-like receptor (SORL1) gene would affect multiple Alzheimer's phenotypes before the clinical onset of symptoms. Four independent samples were analyzed to determine effects of SORL1 genetic risk variants across the lifespan at multiple phenotypic levels: (1) microstructural integrity of white matter using diffusion tensor imaging in two healthy control samples (n=118, age 18-86; n=68, age 8-40); (2) gene expression using the Braincloud postmortem healthy control sample (n=269, age 0-92) and (3) Alzheimer's neuropathology (amyloid plaques and tau tangles) using a postmortem sample of healthy, mild cognitive impairment (MCI) and Alzheimer's individuals (n=710, age 66-108). SORL1 risk variants predicted lower white matter fractional anisotropy in an age-independent manner in fronto-temporal white matter tracts in both samples at 5% family-wise error-corrected thresholds. SORL1 risk variants also predicted decreased SORL1 mRNA expression, most prominently during childhood and adolescence, and significantly predicted increases in amyloid pathology in postmortem brain. Importantly, the effects of SORL1 variation on both white matter microstructure and gene expression were observed during neurodevelopmental phases of the human lifespan. Further, the neuropathological mechanism of risk appears to primarily involve amyloidogenic pathways. Interventions targeted toward the SORL1 amyloid risk pathway may be of greatest value during early phases of the lifespan.

Indexed as

Genetic Predisposition to DiseaseAdolescentAdultAgedAged, 80 and overAgingAlzheimer DiseaseBrainChildChild, PreschoolDiffusion Tensor ImagingFemaleHumansInfantInfant, NewbornLDL-Receptor Related ProteinsLDL-Receptor Related ProteinsMembrane Transport ProteinsRNA, MessengerSORL1 protein, human

Identifiers

PMID24166411
PMCPMC4004725
OpenAlexW1994457811

What OpenQuestion holds

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Registered trials

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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.