Toxic Amyloid-β42 Conformer May Accelerate the Onset of Alzheimer's Disease in the Preclinical Stage

Background: Toxic amyloid-beta protein (A beta) conformers play an important role in the progression of Alzheimer's disease (AD). The ratio of toxic conformer to total A beta(42) in cerebrospinal fluid (CSF) was significantly high in AD and mild cognitive impairment (MCI) due to AD using an enzyme-linked immunosorbent assay kit with a 24B3 antibody. Objective: We compared the toxic A beta(42), conformer at different stages of AD to identify its contribution to AD pathogenesis. Methods: We compared 5 patients with preclinical AD, 11 patients with MCI due to AD, 21 patients with AD, and 5 healthy controls to measure CSF levels of total A beta(42), total tau, tau phosphorylated at threonine 181 (p-tau), and toxic A beta conformers. All were classified using the Clinical Dementia Rating. Cognitive function was assessed using the Japanese version of the Mini-Mental State Examination (MMSE-J). Results: Toxic A beta conformer level was insignificant between groups, but its ratio to A beta(42) was significantly higher in AD than in preclinical AD (p < 0.05). Toxic A beta(42) conformer correlated positively with p-tau (r = 0.67, p < 0.01) and p-tau correlated negatively with MMSE-J (r = -0.38, p < 0.05). Conclusion: Toxic A beta conformer triggers tau accumulation leading to neuronal impairment in AD pathogenesis.

Automated summary

The study compared toxic A beta conformers at different stages of AD, with toxic A beta(42) conformers positively correlated with p-tau in AD, and p-tau negatively correlated with cognitive function, indicating that toxic A beta conformers trigger tau accumulation leading to neuronal impairment in AD pathogenesis.