We review the literature on Tau and TDP-43 proteinopathies in aged human brains and the
relevant underlying pathogenetic cascades. Complex interacting pathways are implicated in
Alzheimer's disease and related dementias (ADRD), wherein multiple proteins tend to
misfold in a manner that is “reactive,” but, subsequently, each proteinopathy may contribute
strongly to the clinical symptoms. Tau proteinopathy exists in brains of individuals across a
broad spectrum of primary underlying conditions—eg, developmental, traumatic, and …