Amyloid beta (Aβ) plaques and neurofibrillary tangles (NFTs) containing aggregates of hyperphosphorylated tau represent the diagnostic pathological lesions present in Alzheimer’s disease (AD) brains. The mechanism of interaction between Aβ plaques and NFTs remains incompletely understood, but both contribute to neurodegeneration in AD. The discovery of mutations causing FTLD-tau in the human gene encoding tau protein has demonstrated amyloid independent tau neurotoxicity [1–3] and tangles, rather than plaques, correlate most closely with the severity of dementia in AD [4]. These observations support the need for further exploration of the mechanistic underpinnings of both Aβ- and tau-mediated neurodegeneration in AD. Here we focus on disease mechanisms relating pathological tau to nuclear dysfunction.
