Alzheimer's disease (AD) is a neurodegenerative disorder primarily affecting regions of the brain responsible for higher cognitive functions. Immunization against ␤-amyloid (A␤) in animal models of AD has been shown to be effective on the molecular level but also on the behavioral level. Recently, we reported naturally occurring autoantibodies against A␤ (NAbs-A␤) being reduced in Alzheimer's disease patients. Here, we further investigated their physiological role: in epitope mapping studies, NAbs-A␤ recognized the mid-/Cterminal end of A␤ and preferentially bound to oligomers but failed to bind to monomers/fibrils. NAbs-A␤ were able to interfere with A␤ peptide toxicity, but NAbs-A␤ did not readily clear senile plaques although early fleecy-like plaques were reduced. Administration of NAbs-A␤ in transgenic mice improved the object location memory significantly, almost reaching performance levels of wild-type control mice. These findings suggest a novel physiological mechanism involving NAbs-A␤ to dispose of proteins or peptides that are prone to forming toxic aggregates.

Using a well-validated assay, we detected reduced α-Syn-nAbs levels in patients with PD compared to patients with AD and HC. The assay did not achieve criteria for use as a diagnostic tool to reliably distinguish PD from HC. Further studies are needed to assess α-Syn-nAbs as a biomarker in PD.