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Transsynaptic transmission, rather than the direct cell-to-cell transmission, may be consistent with the anatomical spreading of TDP-43 aggregations, but cellular mechanisms of transsynaptic transmission of aggregated proteins remain to be elucidated. Moreover, the spreading of TDP-43 inclusions varies among patients and genetic backgrounds, which indicates host-dependent factors for spreading of TDP-43 aggregations. Perturbation of cellular TDP-43 clearance may be a possible factor modifying the aggregation and spreading. This review d
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