Glycogen and amyloid-beta: key players in the shift from neuronal hyperactivity to hypoactivity observed in Alzheimer's disease?

Introduction:Alzheimer’s disease(AD)begins to develop decades prior to its clinical manifestation(Sperling et al.,2011),and while it is the most common form of dementia,as of yet there is no cure.Two of the most researched pathological features contributing to disease development are the extracellular amyloid plaques composed of amyloid-beta proteins(Aβ)and neurofibrillary tangles of tau proteins.Another feature of AD is the progression of early neuronal excitability/hyperactivity to silencing/hypoactivity(Palop and Mucke,2010),with hypoactivity explained by the synaptic failure hypothesis(Selkoe,2002).In vitro and animal model studies have demonstrated that Aβpathology associates with increased excitability of