Molecular mechanisms linking amyloid β toxicity and Tau hyperphosphorylation in Alzheimer׳s disease

• Mitochondrial reactive oxygen species are important in Alzheimer disease pathophysiology.
• Amyloid β and p-Tau toxicities are not independent mechanisms in Alzheimer disease pathophysiology.
• RCAN, p38, CDK5–p25, ApoE, GSK3β, and Pin1 are involved in linking Aβ and p-Tau toxicities.

Neurofibrillary tangles (aggregates of cytoskeletal Tau protein) and senile plaques (aggregates mainly formed by amyloid β peptide) are two landmark lesions in Alzheimer׳s disease. Some researchers have proposed tangles, whereas others have proposed plaques, as primary lesions. For a long time, these were thought of as independent mechanisms. However, experimental evidence suggests that both lesions are intimately related. We review here some molecular pathways linking amyloid β and Tau toxicities involving, among others, glycogen synthase kinase 3β, p38, Pin1, cyclin-dependent kinase 5, and regulator of calcineurin 1. Understanding amyloid β and Tau toxicities as part of a common pathophysiological mechanism may help to find molecular targets to prevent or even treat the disease.

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