PRKN and Alzheimer disease: However, the fact that parkin-associated modification of Tau occurs in the presence of Aβ42 [257] and the recent demonstration that parkin reductions in TS65DN mice (a mouse model of down syndrome [258] in which a triplication of chromosome 21 encoding βAPP occurs in humans) occur before Tau hyperphosphorylation [259] argues in favor of a more selective participation of parkin in Tau modifications taking place in AD.