Alzheimer's disease (AD) is the most common neurodegenerative disorder and accounts for more than 60-80% of all cases of dementia. Loss of pyramidal neurons, extracellular amyloid beta (Abeta) accumulated senile plaques, and neurofibrillary tangles that contain hyperphosphorylated tau constitute the main pathological alterations in AD.Synaptic dysfunction and extrasynaptic N-methyl-D-aspartate receptor (NMDAR) hyperactivation contributes to excitotoxicity in patients with AD. Amyloid precursor protein (APP) and Abeta promoted neurodegeneration develop through the activation of protein kinase signaling cascade in AD. Furthermore, ultimate neuronal death in AD is under control of protein kinases-related signaling pathways. In this chapter, critical check-points within the cross-talk between neuron and protein kinases have been defined regarding the initiation and progression of AD. In this context, amyloid cascade hypothesis, neuroinflammation, oxidative stress, granulovacuolar degeneration, loss of Wnt signaling, Abeta-related synaptic alterations, prolonged calcium ions overload and NMDAR-related synaptotoxicity, damage signals hypothesis and type-3 diabetes are discussed briefly.In addition to clinical perspective of AD pathology, recommendations that might be effective in the treatment of AD patients have been reviewed.
Keywords: Abeta-derived diffusible ligand (ADDL); Alzheimer’s disease (AD); Amyloid beta (Abeta); Amyloid precursor protein (APP); Cytosolic p21-activated kinase (PAK); Ephrin B receptor; N-methyl-D-aspartate receptor (NMDAR); Neurofibrillary tangle (NFT); Tau; Type 3 diabetes.