Amyloid or tau: the chicken or the egg?

Excerpt

Alzheimer’s disease (AD) is characterised pathologically by the widespread brain distribution of two aggregated proteins, amyloid β protein (Aβ) and hyperphosphorylated tau. Both are central to the diagnosis. According to present criteria, this requires the presence of an abundance of plaques containing fibrillar Aβ (so-called senile or amyloid plaques) within the extracellular space of the brain, and a multitude of intraneuronal neurofibrillary tangles, pre-tangles or neuropil threads, and dystrophic neurites within plaques, all containing tau proteins [20, 35]. However, the question as to which of these proteinaceous structures is primary, or indeed whether the presence of one even depends upon, or is triggered by, the presence of the other, remains unanswered. Much of the present evidence favours the formation of Aβ as the primary driving force behind the pathogenesis of AD with tau pathology following as a consequential, or at least secondary, event. However, Braak and Del Tredici [3] argue for a primary deposition of tau, which in turn drives the formation, release and accumulation of Aβ in the form of extracellular plaques. This view is formulated upon two key observations: …