ArticleNeurobiology of disease2026
Human TDP-43 expression worsens FTD-related phenotypes in progranulin-insufficient mice.
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Article in Neurobiology of disease, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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21 authors.
Anna K CookKillion Center for Neurodegeneration and Experimental Therapeutics, Alzheimer's Disease Center, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA; Department of Neurology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
Benjamin LinDepartment of Pathology, Division of Neuropathology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
Yumo SongKillion Center for Neurodegeneration and Experimental Therapeutics, Alzheimer's Disease Center, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA; Department of Biochemistry and Molecular Genetics, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
Kelsey M GreathouseKillion Center for Neurodegeneration and Experimental Therapeutics, Alzheimer's Disease Center, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA; Department of Neurology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
Azariah K KaplelachKillion Center for Neurodegeneration and Experimental Therapeutics, Alzheimer's Disease Center, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA; Department of Neurology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
Mackenzie L LoveKillion Center for Neurodegeneration and Experimental Therapeutics, Alzheimer's Disease Center, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA; Department of Neurology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
Skylar E DavisKillion Center for Neurodegeneration and Experimental Therapeutics, Alzheimer's Disease Center, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA; Department of Neurology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
Anna C StollKillion Center for Neurodegeneration and Experimental Therapeutics, Alzheimer's Disease Center, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA; Department of Neurology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
Justin A HallKillion Center for Neurodegeneration and Experimental Therapeutics, Alzheimer's Disease Center, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA; Department of Neurology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
Ahmad R HakimKillion Center for Neurodegeneration and Experimental Therapeutics, Alzheimer's Disease Center, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA; Department of Neurology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
Jakub F HelKillion Center for Neurodegeneration and Experimental Therapeutics, Alzheimer's Disease Center, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA; Department of Neurology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
Giacynta A VollmerKillion Center for Neurodegeneration and Experimental Therapeutics, Alzheimer's Disease Center, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA; Department of Neurology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
Alexandria C HowardKillion Center for Neurodegeneration and Experimental Therapeutics, Alzheimer's Disease Center, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA; Department of Neurology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
Noelle H CooperKillion Center for Neurodegeneration and Experimental Therapeutics, Alzheimer's Disease Center, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA; Department of Neurology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
Phaedra N ManuelKillion Center for Neurodegeneration and Experimental Therapeutics, Alzheimer's Disease Center, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA; Department of Neurology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
Juliana M EberhardtKillion Center for Neurodegeneration and Experimental Therapeutics, Alzheimer's Disease Center, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA; Department of Neurology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
C Ryan MillerDepartment of Pathology, Division of Neuropathology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
Ashley S HarmsKillion Center for Neurodegeneration and Experimental Therapeutics, Alzheimer's Disease Center, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA; Department of Neurology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
Jeremy H HerskowitzKillion Center for Neurodegeneration and Experimental Therapeutics, Alzheimer's Disease Center, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA; Department of Neurology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
Lindsay F RizzardiKillion Center for Neurodegeneration and Experimental Therapeutics, Alzheimer's Disease Center, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA; Department of Biochemistry and Molecular Genetics, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
Andrew E ArrantKillion Center for Neurodegeneration and Experimental Therapeutics, Alzheimer's Disease Center, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA; Department of Neurology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA. Electronic address: andrewarrant@uabmc.edu.
Funding
XRAY CRYSTALLOGRAPHYP30CA013148 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Omer Jamy · 1985 to 2026
$165.9MUAB Alzheimer's Disease Research CenterP30AG086401 · NIA · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Marissa C Natelson Love · 2024 to 2026
$17.1MMEDICAL SCIENTIST TRAINING PROGRAMT32GM008361 · NIGMS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI YACOUBIAN, TALENE ALENE · 1992 to 2024
$16.8MIdentifying therapeutic targets that confer synaptic resilience to Alzheimer's diseaseR01AG061800 · NIA · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Christopher A. Gaiteri, Jeremy H. Herskowitz · 2018 to 2026
$6.9MCredentialing next-generation human glioma models for precision therapeuticsR01CA258248 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Frank Furnari, Christopher Ryan Miller · 2022 to 2026
$3.0MMechanisms of Thalamocortical Dysfunction and Social Deficits in FTD due to GRN MutationsR01NS128031 · NINDS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Andrew Emmett Arrant · 2022 to 2026
$2.1MTherapeutic targeting mesenchymal transition in newly diagnosed and recurrent GBMR01NS134798 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Frank Furnari, Christopher Ryan Miller · 2024 to 2026
$1.9MTargeting Rho Kinases for Alzheimer's disease TherapeuticsR01AG054719 · NIA · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI HERSKOWITZ, JEREMY H. · 2017 to 2021
$1.9MUAB Training Program In NeuroscienceT32NS095775 · NINDS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Erik D Roberson · 2017 to 2026
$1.6MInteractions between progranulin insufficiency and TDP-43F30AG085889 · NIA · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Anna K Cook · 2024 to 2026
$140kNCI NIH HHS P30 CA013148NCI NIH HHS R01 CA258248NIA NIH HHS F30 AG085889NIA NIH HHS P30 AG086401NIA NIH HHS R01 AG054719NIA NIH HHS R01 AG061800NIGMS NIH HHS T32 GM008361NINDS NIH HHS R01 NS128031NINDS NIH HHS R01 NS134798NINDS NIH HHS T32 NS095775
Abstract
Loss-of-function progranulin (GRN) mutations cause frontotemporal dementia with TDP-43 pathology (FTD-TDP). Nearly all pathogenic GRN mutations cause progranulin haploinsufficiency, but it is unclear how progranulin insufficiency causes FTD-TDP. To address this question, we crossed progranulin-insufficient mice with a human TDP-43 transgenic mouse line (RRID:IMSR_JAX:012836) in which homozygous mice (hTDP++) develop TDP-43 aggregates at an early age, but hemizygous mice (hTDP+) do not develop TDP-43 aggregates. We therefore analyzed the effects of progranulin insufficiency on both hTDP+ and hTDP++ mice. Progranulin insufficiency did not induce TDP-43 aggregation in hTDP+ mice, but interacted with hTDP expression to worsen FTD-related phenotypes. Grn
Indexed as
DNA-Binding ProteinsFrontotemporal DementiaProgranulinsAnimalsDisease Models, AnimalHumansMiceMice, TransgenicPhenotypeDNA-Binding ProteinsGrn protein, mouseProgranulinsTARDBP protein, humanFrontotemporal dementiaProgranulinTDP-43
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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.