ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2022
Protein phosphatase 2A and complement component 4 are linked to the protective effect of APOE ɛ2 for Alzheimer's disease.
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Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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23citing papers in PubMed
3.7field-weighted citation impact, top 6% of its field
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23 citing papers in PubMed, 35 citations in OpenAlex.
- Cell-based polygenic risk scores predict clinical progression and prioritize network-based therapeutic targets in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Fingolimod normalizes metabolic signatures associated with synaptic plasticity and memory in APP/PS1 model: Sphingosine-1-phosphate receptor a therapeutic target for Alzheimer's.Scientific reports · 2026Article
- The Adiponectin-PP2A Pathway Confers Cognitive Benefits of Physical Exercise Against Chronic Stress-Induced Tau Hyperphosphorylation in the Hippocampus.Aging cell · 2026Article
- Proteomic profiling of olfactory exfoliates from people with subjective cognitive complaints reveal networks of olfactory biomarkers of cognitive performance.Frontiers in aging neuroscience · 2026Article
- APOE4 Exacerbates Cerebral Tau Pathology Through Cholesterol-Induced Degradation of Phosphatase in Atherosclerosis.CNS neuroscience & therapeutics · 2025Article
- Genome-wide association studies of Alzheimer's disease and related disorders stratified by sex, onset age, and Apolipoprotein E genotype reveal novel risk loci in African Americans.Alzheimer's research & therapy · 2025Article
- Analysis of human brain RNA-seq data reveals combined effects of 4 types of RNA modifications and 18 types of programmed cell death on Alzheimer's disease.Journal of translational medicine · 2025Article
- Rescue of hippocampal synaptic plasticity and memory performance by Fingolimod (FTY720) in APP/PS1 model of Alzheimer's disease is accompanied by correction in metabolism of sphingolipids, polyamines, and phospholipid saturation composition.bioRxiv : the preprint server for biology · 2025Article
- Multi-functional role of apolipoprotein E in neurodegenerative diseases.Frontiers in aging neuroscience · 2025Review
- The role of lipid metabolism in cognitive impairment.Arquivos de neuro-psiquiatria · 2025Review
- Article
- APOE genotype-specific methylation patterns are linked to Alzheimer disease pathology and estrogen response.Translational psychiatry · 2024Article
- Immune receptors and aging brain.Bioscience reports · 2024Review
- ATP1A3 as a target for isolating neuron-specific extracellular vesicles from human brain and biofluids.Science advances · 2023Article
- Social defeat stress induces genome-wide 5mC and 5hmC alterations in the mouse brain.G3 (Bethesda, Md.) · 2023Article
- Immortalized hippocampal astrocytes from 3xTg-AD mice, a new model to study disease-related astrocytic dysfunction: a comparative review.Neural regeneration research · 2023Review
- Article
- DIA-based technology explores hub pathways and biomarkers of neurological recovery in ischemic stroke after rehabilitation.Frontiers in neurology · 2023Article
- APOE E4 is associated with impaired self-declared cognition but not disease risk or age of onset in Nigerians with Parkinson's disease.NPJ Parkinson's disease · 2022Article
- ApoE in Alzheimer's disease: pathophysiology and therapeutic strategies.Molecular neurodegeneration · 2022Review
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Authors and funding
21 authors at 7 institutions in 1 country.
Gyungah R JunDepartment of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, Massachusetts, USA.
Yang YouDepartment of Pharmacology & Experimental Therapeutics, Boston University School of Medicine, Boston, Massachusetts, USA.
Congcong ZhuDepartment of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, Massachusetts, USA.
Gaoyuan MengDepartment of Veterans Affairs Medical Center, Bedford, Massachusetts, USA.
Jaeyoon ChungDepartment of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, Massachusetts, USA.
Rebecca PanitchDepartment of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, Massachusetts, USA.
Junming HuDepartment of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, Massachusetts, USA.
Weiming XiaDepartment of Pharmacology & Experimental Therapeutics, Boston University School of Medicine, Boston, Massachusetts, USA.
Alzheimer's Disease Genetics Consortium
David A BennettRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, USA.
Tatiana M ForoudDepartment of Medical and Molecular Genetics, Indiana University, Indianapolis, Indiana, USA.
Li-San WangPenn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Jonathan L HainesDepartment of Population & Quantitative Health Sciences, Case Western Reserve University, Cleveland, Ohio, USA.
Richard MayeuxTaub Institute on Alzheimer's Disease and the Aging Brain, Gertrude H. Sergievsky Center Department of Neurology, Columbia University, New York, New York, USA.
Margaret A Pericak-VanceJohn P. Hussman Institute for Human Genomics, Department of Human Genetics, and Dr. John T. Macdonald Foundation, University of Miami, Miami, Florida, USA.
Gerard D SchellenbergPenn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Rhoda AuDepartment of Neurology, Boston University School of Medicine, Boston, Massachusetts, USA.
Kathryn L LunettaDepartment of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA.
Tsuneya IkezuDepartment of Pharmacology & Experimental Therapeutics, Boston University School of Medicine, Boston, Massachusetts, USA.
Thor D SteinDepartment of Veterans Affairs Medical Center, Bedford, Massachusetts, USA.
Lindsay A FarrerDepartment of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, Massachusetts, USA.
Boston University · USUniversity of Pennsylvania · USCase Western Reserve University · USColumbia University · USIndiana University – Purdue University Indianapolis · USRush University Medical Center · USUniversity of Miami · 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
$119.8MTRIAL OF VALPROATE TO ATTENUATE THE PROGRESSION OF ADU01AG010483 · NIA · UNIVERSITY OF ROCHESTER · PI AISEN, PAUL S. · 1991 to 2012
$116.2MNATIONAL ALZHEIMERS COORDINATING CENTER (NACC)U01AG016976 · NIA · UNIVERSITY OF WASHINGTON · PI KUKULL, WALTER ANTHONY · 1999 to 2020
$72.8MSmartphone-Based "Burst" Cognitive AssessmentsP01AG003991 · NIA · WASHINGTON UNIVERSITY · PI JOHN MORRIS · 1985 to 2026
$69.5MTDP-43 Loss-of-Function: Biology to BiomarkersP01AG019724 · NIA · UNIVERSITY OF PENNSYLVANIA · PI Jennifer Merrilees · 2002 to 2026
$67.2MAlzheimer's Disease Genetics ConsortiumU01AG032984 · NIA · UNIVERSITY OF PENNSYLVANIA · PI SCHELLENBERG, GERARD DAVID · 2009 to 2024
$60.4MTHERAPEUTIC EFFECTS OF INTRA-NASAL INSULIN DETEMIRP50AG005136 · NIA · UNIVERSITY OF WASHINGTON · PI GRABOWSKI, THOMAS J. · 1985 to 2019
$57.2MVIRUS-INDUCED BRAIN PATHOLOGYP50AG005131 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BREWER, JAMES B · 1985 to 2018
$55.4MWASHINGTON UNIVERSITY ALZHEIMERS DISEASE RESEARCH CENTERP50AG005681 · NIA · WASHINGTON UNIVERSITY · PI FAGAN, ANNE · 1985 to 2019
$52.1MThe natural history of AB accumulation in preclinical ADP01AG026276 · NIA · WASHINGTON UNIVERSITY · PI MORRIS, JOHN · 2005 to 2025
$49.5MSUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI LEURGANS, SUE E. · 1991 to 2020
$49.1MSatellite Diagnostic and Treatment Clinic CoreP50AG008702 · NIA · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI DE JAGER, PHILIP L · 1989 to 2019
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Abstract
introductionThe apolipoprotein E (APOE) ɛ2 allele reduces risk against Alzheimer's disease (AD) but mechanisms underlying this effect are largely unknown.
methodsWe conducted a genome-wide association study for AD among 2096 ɛ2 carriers. The potential role of the top-ranked gene and complement 4 (C4) proteins, which were previously linked to AD in ɛ2 carriers, was investigated using human isogenic APOE allele-specific induced pluripotent stem cell (iPSC)-derived neurons and astrocytes and in 224 neuropathologically examined human brains.
resultsPPP2CB rs117296832 was the second most significantly associated single nucleotide polymorphism among ɛ2 carriers (P = 1.1 × 10 DISCUSSION: PP2A may be linked to classical complement activation leading to AD-related tau pathology.
Indexed as
Alzheimer DiseaseApolipoprotein E2Apolipoprotein E4Apolipoproteins EComplement C4Genome-Wide Association StudyHumansProtein Phosphatase 2tau ProteinsApolipoprotein E2Apolipoprotein E4Apolipoproteins EComplement C4Protein Phosphatase 2tau ProteinsAlzheimer's diseaseapolipoprotein EC4Bhuman induced pluripotent stem cellsPPP2CBtau protein
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