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• W4200505280 abstract "Abstract Background Behavioral variant frontotemporal dementia (bvFTD) is a common form of younger-onset dementia with a proportion of cases overlapping pathologically and genetically with amyotrophic lateral sclerosis (ALS). Previous studies have identified that the human endogenous retrovirus K (HERV-K) is elevated in ALS serum and is associated with ALS TDP-43 pathology. In contrast, little is known about HERV-K changes in bvFTD. Here, we investigated the possible role of HERV-K in bvFTD. Methods We measured the HERV-K env gene in sporadic bvFTD ( N = 63), sporadic ALS ( N = 89), and control ( N = 21) serum by ddPCR. We also analyzed HERV-K env , by qPCR, and the HERV-K reverse transcriptase protein, by confocal immunofluorescence microscopy, in the disease-affected superior frontal cortex of bvFTD with TDP-43 pathology. Results Here, we show that HERV-K env levels are significantly elevated ( P = 3.5 × 10 −6 ) in bvFTD compared to control serum, differentiating cases with an AUC value of 0.867. HERV-K env levels are also specifically elevated in the superior frontal cortex of bvFTD with TDP-43 pathology, with the HERV-K reverse transcriptase protein and TDP-43 deposit localized to the neuronal cytoplasm. Furthermore, in a neuronal cell line overexpression of TDP-43 induces HERV-K env transcription. Conclusions These results suggest that manifestation of HERV-K is associated with bvFTD TDP-43 pathology. Analysis of HERV-K in bvFTD may provide insight into an unrecognized but targetable perturbed pathology." @default.
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• W4200505280 date "2021-12-09" @default.
• W4200505280 modified "2023-10-15" @default.
• W4200505280 title "Pathological manifestation of human endogenous retrovirus K in frontotemporal dementia" @default.
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• W4200505280 doi "https://doi.org/10.1038/s43856-021-00060-w" @default.
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