Misfolded amyloid-beta conformational variants(strains)as drivers of Alzheimer's disease neuropathology
Salvatore Saieva
Rodrigo Morales
Abstract：Pathological and clinical variability in Alzheimer's disease (AD): AD is clinically characterized by progressive memory loss and cognitive impairment. From a pathological point of view, the main features of AD are the deposition of amyloid plaques (composed of amyloid-beta, Aβ) and neurofibrillary tangles containing hyperphosphorylated Tau in the brain, accompanied by neuronal and synaptic loss, neuroinflammation and brain atrophy (Jellinger, 2022). Regardless of these common traits, growing evidence shows increased heterogeneity in the brain of AD patients considering both clinical manifestations and pathological features. Mounting evidence points to the variable conformations that misfolded Aβ can acquire (referred to as 'Aβ strains') as the source of this pathological and clinical variability. The existence of Aβ strains is relevant as they may also predict prognosis and responses to treatments. The concept of Aβ strains is analogous to that coined for infectious prion strains, which are further defined below (Jellinger, 2022).
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Publication Date：2025-11-27
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：2( 3219-3220 )