A3 Alzheimer's (amyloid plaques, tau tangles)

Title

Alzheimer's disease is modeled as a protein aggregation cascade that progresses from extracellular beta-amyloid accumulation to hyperphosphorylation and aggregation of intracellular tau protein, with synaptic loss and neuronal death as final consequences. The aggregation of beta-amyloid follows a nucleation-elongation kinetics (Finke-Watzky type), balanced by its physiological clearance; When production exceeds the clearance capacity, the aggregates promote the activation of kinases that hyperphosphorylate tau, which in turn aggregates forming neurofibrillary tangles. Both cascades converge in a reduction in synaptic density (extension of the S variable defined at E14) and, finally, in neuronal death proportional to the load of tangles, which clinically translates into progressive cognitive deterioration.

ID:4285