Monoclonal antibodies selective for α-synuclein oligomers/protofibrils recognize brain pathology in Lewy body disorders and α-synuclein transgenic mice with the disease-causing A30P mutation.

摘要: Inclusions of intraneuronal alpha-synuclein (α-synuclein) can be detected in brains patients with Parkinson's disease and dementia Lewy bodies. The aggregation α-synuclein is a central feature the pathogenesis. Among different species, large oligomers/protofibrils have particular neurotoxic properties should therefore suitable as both therapeutic diagnostic targets. Two monoclonal antibodies, mAb38F mAb38E2, high affinity strong selectivity for oligomers were generated. These which do not bind amyloid-beta or tau, recognize body pathology from bodies detect earlier transgenic mice than linear epitope antibodies. An oligomer-selective sandwich ELISA, based on mAb38F, was set up to analyze brain extracts mice. overall levels found increase age these mice, although displayed interindividual variation. Upon subcellular fractionation, higher could endoplasmic reticulum around when behavioral disturbances develop. In summary, our novel antibodies relevant important tools further explore pathogenic mechanisms disorders. Moreover, they potential candidates immunotherapy reagents an assay assess biomarker.