Our data show region-dependent synergistic interactions, with exacerbated metabolic deficits, demyelination, gliosis, tau pathology and neurodegeneration in SHRSP/FAD rats, which is consistent with clinical and neuropathological data suggesting that coexistence of subclinical AD and SVD pathologies may lower the threshold for dementia risk (Fischer et al., 1991). Here, MAPT is linked to Alzheimer disease.