MAPT and tauopathy: Further, it has been recently shown that APOE4 markedly exacerbates tau-mediated neurodegeneration in a mouse model of tauopathy [23]; this finding, and the observation that tauopathy associated with frontotemporal dementia is associated with increased apoE4 allele frequency, suggest that the involvement of apoE4 in tauopathy may be independent of Aβ [37, 38].