Human genetic of dementia sheds light on new roles of APP, APOE, and MAPT

Human genetic of dementia sheds light on new roles of APP, APOE, and MAPT

Yo Higuchi, Takeshi Ikeuchi

Department of Molecular Genetics, Brain Research Institute, Niigata University

Amyloid-β （Aβ）, apoE and tau are major players in the pathogenesis underlying neurodegenerative dementia.　In autosomal dominant Alzheimer’s disease （AD）, initial pathological event is Aβ deposition caused by APP/PSEN mutation. Recently, Christchurch variant of APOE was reported to show a protective effect against Aβ-induced tau accumulation.　In sporadic AD, tau accumulation in entorhinal cortex may be an initial event.　Aβ deposition which is largely affected by APOE genotypes enhances the spreading tau pathology in AD brain.　Protective effects of APOE ε2 and APP p.A673T variant against Aβ deposition have been demonstrated.　MAPT mutations directly cause tau accumulation, which leads to hereditary tauopathy.　In some forms of sporadic tauopathies, APOE genotypes may modify tau accumulation.　Collectively, human genetics of dementia sheds light on the new roles of Aβ, ApoE, and tau.

Address correspondence to Dr. Takeshi Ikeuchi, Department of Molecular Genetics, Brain Research Institute, Niigata University （1-757 Asahimachi, Niigata 951-8585, Japan）