Oligomers and Neurodegeneration: New Evidence

Abstract

In the last few months new results in Alzheimer's (AD) and Parkinson's disease (PD) have converged, attracting attention to oligomer species of misfolded proteins, β-amyloid (Aβ and α-synuclein (α-Syn), in the pathogenesis. The high affinity for Aβ protofibrils and oligomers of lecanemab, an antibody recently approved as a disease-modifying drug in AD, and the identification of Aβ-oligomers in blood samples as early biomarkers in subjects with cognitive decline, indicate the oligomers as a therapeutic target and diagnostic tool in AD. α-Syn oligomers were identified by new histopathological techniques in the hippocampus and visual cortex of PD subjects with a distribution distinct from the Lewy body pathologies but associated with cognitive impairment; these species purified from PD brain were highly neurotoxic. In a PD experimental model, we confirmed the presence of α-Syn oligomers associated with cognitive decline and sensitive to drug treatment.