Does dysregulation of the Notch and wingless/Wnt pathways underlie the pathogenesis of Alzheimer's disease?

Alzheimer's disease is characterized by the presence of neurofibrillary tan gles and senile neuritic plaques in the brain. Tangles are aggregates of pa ired helical filaments composed of the microtubule-associated protein, tau, in a hyperphosphorylated state. Senile plaques have a core of amyloid beta -peptide derived by proteolysis of the amyloid precursor protein. A major h urdle in defining the pathogenic mechanisms in Alzheimer's disease is to un derstand how both amyloid p-peptide deposition and paired helical filament formation are biochemically linked. Recent genetic discoveries provide some clues, suggesting that components of two developmentally important signall ing pathways, Notch and wingless, or the vertebrate homologue of wingless, Wnt, are involved.