By the same mechanism, a protein misfolding disorder may be related to aggregation of amyloid plaques.
Endogenous metals like zinc contribute to the aggregation of β-amyloid plaques and knocking out zinc transporters (ZnT-3) in mice leads to significantly fewer and smaller plaques and lower zinc concentrations in the hippocampus [13], [14].
Increased levels of Aβ leading to the accumulation and aggregation of Aβ into plaques, is one of the most extensively studied pathologies in AD.
Ineffective resolution of protein misfolding and unmitigated protein aggregation can lead to formation of plaques, fibrils, and other aggregated species encountered in neurodegenerative diseases.
To date, most treatment strategies have tried to target the production or clearance of Aβ or manipulate tau aggregation, while the secondary consequence of plaques and tangles remains largely unaddressed.
Recent studies suggest that BuChE is present in key brain areas and may also influence the aggregation of neuritic β-amyloid (Aβ) plaques to form the neurofibrillary plaques causing [13 15].
From animal models of AD [ 5, 6] or histochemical analysis of human brain serial sections [ 7], one may conclude that this response is triggered by amyloid plaques, and a number of studies have reported aggregation of activated microglia around amyloid plaques in animal [ 5] and human brain [ 8– 10].
Further, phosphorylated Aβ aggregates could serve as endogenous seeds triggering further aggregation of soluble, extracellular Aβ into plaques in the brain.
However, the failure mechanism under tensile loading has not been elucidated yet, despite its importance for the understanding of key mechanical properties of amyloid fibrils and plaques as well as the growth and aggregation of amyloids into long fibers and plaques.
