biostudies-literatureRessler HWNational Institute of Neurological Disorders and StrokeTau ConsortiumNIA NIH HHSCurePSPStuart KatzNINDS NIH HHSJane MartinNational Institute on Aging135https://www.ebi.ac.uk/biostudies/studies/S-EPMC11330133biostudies-literatureUnknown12(1)Progressive supranuclear palsy (PSP) is a neurodegenerative movement and cognitive disorder characterized by abnormal accumulation of the microtubule-associated protein tau in the brain. Biochemically, inclusions in PSP are enriched for tau proteoforms with four microtubule-binding domain repeats (4R), an isoform that arises from alternative tau pre-mRNA splicing. While preferential aggregation and reduced degradation of 4R tau protein is thought to play a role in inclusion formation and toxicity, an alternative hypothesis is that altered expression of tau mRNA isoforms plays a causal role. This stems from the observation that PSP is associated with common variation in the tau gene (MAPT) at the 17q21.31 locus which contains low copy number repeats flanking a large recurrent genomic inversActa neuropathologica communicationsMAPT haplotype-associated transcriptomic changes in progressive supranuclear palsy.PMC11330133U54NS115266R01 NS086736P30 AG066514K01AG070326R01 AG054008T35 AG067578U19 AG074879685–2023-06RF1NS095252R01AG054008U54 NS123743R01NS086736P30AG066514T35AG067578U54 NS115266R01 AG062348RF1 NS095252R01AG062348U54NS123743685-2023-06K01 AG070326Dickson DWRessler HWBabrowicz BKandoi SVialle RACrary JFFarrell KHumphrey JRaj TErtekin-Taner NfalseMAPT haplotype-associated transcriptomic changes in progressive supranuclear palsy.Progressive supranuclear palsy (PSP) is a neurodegenerative movement and cognitive disorder characterized by abnormal accumulation of the microtubule-associated protein tau in the brain. Biochemically, inclusions in PSP are enriched for tau proteoforms with four microtubule-binding domain repeats (4R), an isoform that arises from alternative tau pre-mRNA splicing. While preferential aggregation and reduced degradation of 4R tau protein is thought to play a role in inclusion formation and toxicity, an alternative hypothesis is that altered expression of tau mRNA isoforms plays a causal role. This stems from the observation that PSP is associated with common variation in the tau gene (MAPT) at the 17q21.31 locus which contains low copy number repeats flanking a large recurrent genomic invers2024-01-01T00:00:00Z2024 Aug2026-06-02T04:45:40.666Z2025-04-04T08:22:41.414ZS-EPMC113301333915416310.1186/s40478-024-01839-3