ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2022
Progranulin mutations in clinical and neuropathological 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 19 papers, 1 of them a synthesis that pooled it.
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19citing papers in PubMed, 1 pooled it
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- A genome-wide search for pleiotropy in more than 100,000 harmonized longitudinal cognitive domain scores.Molecular neurodegeneration · 2023Pooled it
- Brain-Wide Multi-Trait Genetic Integration Implicates Lysosomal and Metabolic Axes Linking Visual Disturbance and Alzheimer's Disease.Molecular neurobiology · 2026Article
- ARID5A RNA-binding coordinates microglial defense and ferroptosis in iPSC-derived models.Nature communications · 2026Article
- Nanoparticles that target nonamyloid and nontau pathways in Alzheimer's disease.Discover nano · 2026Review
- Comprehensive adjudication identifies 111 high-confidence loci for Alzheimer's disease and related dementias.medRxiv : the preprint server for health sciences · 2026Article
- Progranulin deficiency in the brain activates an insulin signaling pathway that may promote neurodegeneration.iScience · 2026Article
- Phenotypic diversity of frontotemporal lobar degeneration in two novel GRN variants from Colombia.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Ablation of progranulin augments microglial activation and accelerates prion progression.Acta neuropathologica communications · 2025Article
- CSF proteogenomics implicates novel proteins and humoral immunity in Alzheimer's disease risk.medRxiv : the preprint server for health sciences · 2025Article
- PGRN as an emerging regulator of lipid metabolism in neurodegenerative diseases.Communications biology · 2025Review
- LATE-NC Stage 3: a diagnostic rubric to differentiate severe LATE-NC from FTLD-TDP.Acta neuropathologica · 2025Article
- Biomarker identification for Alzheimer's disease through integration of comprehensive Mendelian randomization and proteomics data.Journal of translational medicine · 2025Article
- ABCA7-dependent induction of neuropeptide Y is required for synaptic resilience in Alzheimer's disease through BDNF/NGFR signaling.Cell genomics · 2024Article
- Progranulinopathy: A diverse realm of disorders linked to progranulin imbalances.Cytokine & growth factor reviews · 2024Review
- Characterization of Progranulin Gene Mutations in Portuguese Patients with Frontotemporal Dementia.International journal of molecular sciences · 2023Article
- Combined analysis of single-cell and bulk RNA sequencing reveals the expression patterns of circadian rhythm disruption in the immune microenvironment of Alzheimer's disease.Frontiers in immunology · 2023Article
- TDP-43 Proteinopathy and Tauopathy: Do They Have Pathomechanistic Links?International journal of molecular sciences · 2022Review
- Progranulin mutations in clinical and neuropathological Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2022Article
- Understanding recent advances in non-amyloid/non-tau (NANT) biomarkers and therapeutic targets in Alzheimer's disease.Alzheimer's & dementia (New York, N. Y.)Article
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Authors and funding
21 authors at 11 institutions in 3 countries.
Badri N VardarajanTaub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, New York, USA.
Dolly Reyes-DumeyerTaub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, New York, USA.
Angel L PirizTaub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, New York, USA.
Rafael A LantiguaTaub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, New York, USA.
Martin MedranoSchool of Medicine, Pontificia Universidad Catolica Madre y Maestra (PUCMM), Santiago, Dominican Republic.
Diones RiveraDepartment of Neurology, CEDIMAT, Plaza de la Salud, Santo Domingo, Dominican Republic.
Ivonne Z Jiménez-VelázquezDepartment of Medicine, University of Puerto Rico School of Medicine, San Juan, Puerto Rico, USA.
Eden MartinThe John P. Hussman Institute for Human Genomics, and Dr. John T. Macdonald Foundation Department of Human Genetics, Miami, Florida, USA.
Margaret A Pericak-VanceThe John P. Hussman Institute for Human Genomics, and Dr. John T. Macdonald Foundation Department of Human Genetics, Miami, Florida, USA.
William BushDepartment of Biostatistics and Epidemiology, Case Western Reserve University, Cleveland, Ohio, USA.
Lindsay FarrerBoston University School of Medicine, Boston, Massachusetts, USA.
Jonathan L HainesDepartment of Biostatistics and Epidemiology, Case Western Reserve University, Cleveland, Ohio, USA.
Li-San WangSchool of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Yuk Yee LeungSchool of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Gerard SchellenbergSchool of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Walter KukullDepartment of Epidemiology, School of Public Health, University of Washington, Seattle, Washington, USA.
Philip De JagerTaub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, New York, USA.
David A BennettRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, USA.
Julie A SchneiderRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, USA.
Alzheimer's Disease Sequencing Project
Richard MayeuxTaub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, New York, USA.
NewYork–Presbyterian Hospital · USUniversity of Pennsylvania · USCase Western Reserve University · USDr. John T. Macdonald Foundation · USRush University Medical Center · USBoston University · USColumbia University · USInstituto Tecnológico de Santo Domingo · DOPontificia Universidad Católica Madre y Maestra · DOUniversity of Puerto Rico System · PRUniversity of Washington · US
Funding
Large Scale Sequencing and Analysis of GenomesU54HG003067 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GABRIEL, STACEY, LANDER, ERIC S · 2004 to 2015
$568.6MLarge Scale Genome SequencingU54HG003079 · NHGRI · WASHINGTON UNIVERSITY · PI DUTCHER, SUSAN K · 2004 to 2016
$445.7MThe Human Genome Sequencing CenterU54HG003273 · NHGRI · BAYLOR COLLEGE OF MEDICINE · PI GIBBS, RICHARD A · 2004 to 2015
$341.3MNational 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
$119.8MNATIONAL ALZHEIMERS COORDINATING CENTER (NACC)U01AG016976 · NIA · UNIVERSITY OF WASHINGTON · PI KUKULL, WALTER ANTHONY · 1999 to 2020
$72.8MARIC Neurocognitive Study (ARIC-NCS) Renewal 2023-2028U01HL096812 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI JOSEF CORESH, THOMAS H MOSLEY · 2010 to 2026
$65.7MAlzheimer's Disease Genetics ConsortiumU01AG032984 · NIA · UNIVERSITY OF PENNSYLVANIA · PI SCHELLENBERG, GERARD DAVID · 2009 to 2024
$60.4MNew York Center for Collaborative Research In Common Disease Genomics: Genome Aggregation and Joint Variant Calling for CCDG Freeze2UM1HG008901 · NHGRI · NEW YORK GENOME CENTER · PI MANIATIS, THOMAS P, WIGLER, MICHAEL H · 2016 to 2020
$56.6MSUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI LEURGANS, SUE E. · 1991 to 2020
$49.1MEPIDEMIOLOGY OF NEURAL RESERVE AND NEUROBIOLOGY IN AGINGR01AG017917 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 2001 to 2023
$43.3MTHE NIA GENETICS OF ALZHEIMER'S DISEASE DATA STORAGE SITEU24AG041689 · NIA · UNIVERSITY OF PENNSYLVANIA · PI LI-SAN WANG · 2012 to 2026
$42.3MFurthering scientific understanding of mechanisms underlying resilience to the effects of AD pathology by incorporating state of the art quantification of gliosis, inflammation, & synaptic toxicityU01AG006781 · NIA · UNIVERSITY OF WASHINGTON · PI CRANE, PAUL K, LARSON, ERIC B · 1986 to 2020
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Abstract
introductionProgranulin (GRN) mutations occur in frontotemporal lobar degeneration (FTLD) and in Alzheimer's disease (AD), often with TDP-43 pathology.
methodsWe determined the frequency of rs5848 and rare, pathogenic GRN mutations in two autopsy and one family cohort. We compared Braak stage, β-amyloid load, hyperphosphorylated tau (PHFtau) tangle density and TDP-43 pathology in GRN carriers and non-carriers.
resultsPathogenic GRN mutations were more frequent in all cohorts compared to the Genome Aggregation Database (gnomAD), but there was no evidence for association with AD. Pathogenic GRN carriers had significantly higher PHFtau tangle density adjusting for age, sex and APOE ε4 genotype. AD patients with rs5848 had higher frequencies of hippocampal sclerosis and TDP-43 deposits. Twenty-two rare, pathogenic GRN variants were observed in the family cohort. DISCUSSION: GRN mutations in clinical and neuropathological AD increase the burden of tau-related brain pathology but show no specific association with β-amyloid load or AD.
Indexed as
Alzheimer DiseaseFrontotemporal Lobar DegenerationDNA-Binding ProteinsHumansIntercellular Signaling Peptides and ProteinsMutationProgranulinsDNA-Binding ProteinsIntercellular Signaling Peptides and ProteinsProgranulinsAlzheimer's diseaseneuropathologyprogranulinTDP43
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