Editing Progressive supranuclear palsy (section)

=== Genetic Mechanisms in PSP-RS ===
Although there is a strong correlation between the H1 haplotype and PSP, the exact molecular mechanism remains unclear. Some individuals with PSP-RS have reported a family history of the disease, suggesting the possibility that genetic factors, such as the H1 haplotype, may contribute to inherited susceptibility in certain cases.<ref name=":11" /><ref name=":15">{{Cite journal |last1=Wen |first1=Yafei |last2=Zhou |first2=Yafang |last3=Jiao |first3=Bin |last4=Shen |first4=Lu |date=2021 |title=Genetics of Progressive Supranuclear Palsy: A Review |journal=Journal of Parkinson's Disease |volume=11 |issue=1 |pages=93–105 |doi=10.3233/JPD-202302 |issn=1877-718X |pmc=7990399 |pmid=33104043}}</ref> The PSP-RS subtype is known for a buildup of the 4R tau protein, which does not dissolve properly and forms insoluble aggregates in the brain. In healthy brains, there is typically a balanced ratio of 3-repeat (3R) and 4-repeat (4R) tau isoforms, resulting from the regulated inclusion or exclusion of exon 10 on the ''MAPT'' gene.<ref name=":11" /> Inclusion of exon 10 promotes the production of 4R tau, while its exclusion favors 3R tau.<ref name=":11" /><ref name=":15" /> In PSP-RS, this balance is disrupted. Certain genetic variations in MAPT, most notably the H1/H1 haplotype, are associated with increased inclusion of exon 10, leading to elevated levels of 4R tau relative to 3R tau.<ref name=":11" /> The resulting overproduction of 4R tau is believed to contribute to the pathological accumulation of tau aggregates observed in PSP-RS.