Deregulation of these kinases, such as hyperactivation of Cdk5 in response to neuronal insults (e.g., oxidative stress, A-beta toxicity, glutamate toxicity), leads to accumulation of hyperphosphorylated cytoskeletal proteins in neuronal perikarya, tangles of phospho-tau, and aggregated phosphorylated neurofilaments, pathological hallmarks of AD, ALS, and dementia with Lewy bodies [90, 91]. Here, MAPT is linked to Alzheimer disease.