Role for cell death pathway in Alzheimer’s disease

Human neurons transplanted into mice with amyloid plaques die by necroptosis A central, longstanding problem in the study of Alzheimer’s disease (AD) has been an inability to fully recapitulate the biochemical and neuropathological hallmarks of the disease in mouse models, which are important tools of biomedical research. These hallmarks include extracellular plaques of aggregated amyloid-β (αβ), intraneuronal neurofibrillary tangles composed of hyperphosphorylated tau protein, and the loss of neurons. Although some progress has been made in this area ( 1 , 2 ), much work remains to be done. On page 1176 of this issue, Balusu et al. ( 3 ) report a mouse model that results in the generation of AD-like tau pathology and neuronal death in a manner that depends on both the presence of amyloid pathology and transplanted human neurons. The findings suggest an explanation for why it has been challenging to produce αβ-dependent tau pathology and neurodegeneration in mouse models. The work also provides evidence for the importance of a cell death pathway in AD that may be therapeutically tractable.