In Alzheimer disease, the amyloid-β peptide (Aβ) accumulates in the brain as insoluble plaque and soluble oligomers (Aβo). The early accumulation of Aβ, in turn, triggers synaptic damage, inflammatory reaction, and pathological tau with cognitive impairment. Therapeutic development efforts have concentrated on limiting Aβ cleavage from amyloid precursor protein by secretase inhibition
1 or on promoting its clearance by active or passive immunization.
2 One alternative approach is to limit the toxic effects of accumulated Aβ rather than its level. Although Aβo can assume a range of different species, evidence has shown that multiple forms of Aβo are damaging, either directly or in concert with microglia.
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