. A novel temporal-predominant neuro-astroglial tauopathy associated with TMEM106B gene polymorphism in FTLD/ALS-TDP. Brain Pathol. 2020 Dec 12;:e12924. PubMed.

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  1. In frontotemporal dementia, tau and TDP43 rarely appear together. People with #FTLD-TDP and TMEM106B polymorphism A/A have an odds ratio of 13.9 (crude) or 31.3 (multivariate) to develop a distinct 4R tauopathy.

    We investigated 90 FTLD-TDP cases—all types, genetic and sporadic. Sixteen had a singular temporal-predominant neuroglial tauopathy. In the population, one-third of people have a TMEM106B A/A genotype; however, 93.7 percent of FTLD-TDP cases with this tauopathy had an A/A genotype. This singular tauopathy involves neurons and glia, is 4-repeat tau, and shows many tau post-translational modifications.

    The hot spot is the inferior temporal gyrus. Tau and TDP-43 inclusions do NOT overlap. The findings were validated in an independent series from Gabor Kovacs and colleagues. I am unaware of another genetic polymorphism linked to TDP43 and tau comorbidity.

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