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Familial globular glial tauopathy linked to MAPT mutations: Molecular neuropathology and seeding capacity of a prototypical mixed neuronal and glial tauopathy

Acta Neuropathologica Jan 14, 2020

Ferrer I, Andrés-Benito P, Zelaya MV, et al. - Current research concentrated on four genetic globular glial tauopathy (GGT) cases from two unrelated families bearing the P301T mutation in MAPT and one case of sporadic GGT (sGGT) and one case of GGT related to MAPT K317M mutation for comparative views. Phospho-tau's clinical and neuropathological manifestations and biochemical profiles are subject to individual differences in patients with the same mutation, even in carriers of the same family regardless of the onset age, gender and duration of the disease. Eventually, unilateral inoculation of sarkosyl-insoluble fractions of GGT homogenates from GGT related to MAPT P301T, sGGT, and GGT related to MAPT K317M mutation in the hippocampus, corpus callosum, or caudate/putamen in wild-type mice produces seeding, and time- and region-dependent spreading of phosphorylated, non-oligomeric, and non-truncated 4Rtau and 3Rtau, without GAIs and GOIs but only of coiled bodies. Such studies show the significance of host tau strains in modulating cell vulnerability and phospho-tau aggregate phenotypes.
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