科研之友
微信
新浪微博
Facebook
分享链接
摘要
Recent evidence suggests that soluble oligomeric amyloid-beta (A beta) assemblies are critically involved in the pathogenesis of Alzheimer%26apos;s disease (AD). We have generated a conformation-dependent monoclonal antibody (9D5) that selectively recognizes low-molecular weight A beta(pE3) oligomers, and demonstrated its diagnostic and therapeutic potential. Here, we further characterize the specificity of this antibody by evaluating a spectrum of neurodegeneration-related protein deposits for cross-reactivity, and by comparing the staining pattern of 9D5 with a generic A beta antibody that targets a linear epitope (mAb NT244), and with another conformation-dependent A beta antibody that selectively labels amyloid fibrils of various molecular weights (pAb OC). The 9D5 antibody does not cross-react with other aggregated protein deposits in brains of progressive supranuclear palsy, corticobasal degeneration, argyrophilic grain disease, Pick%26apos;s disease, Parkinson%26apos;s disease, dementia with Lewy bodies, multiple system atrophy, frontotemporal lobar degeneration or amyotrophic lateral sclerosis with TDP-43 inclusions, Creutzfeldt-Jakob disease, and vessel changes in Binswanger encephalopathy, demonstrating the specificity of 9D5 for A beta deposits. While NT244 and OC showed a comparable plaque load, 9D5 detected only approximately 15% of the total A beta plaque load in the entorhinal cortex, the CA1 region, and the temporal neocortex. Our study further supports a possible therapeutic advantage of 9D5 by the highly specific recognition of an epitope found only in oligomeric assemblies of A beta(pE3) of AD patients. Moreover, selective binding to only a pathogenetically relevant fraction of A beta deposits serves as rationale for passive immunization with 9D5-derivatives by limiting potential side effects of vaccination due to dissolvement of existing amyloid deposits.
- 出版日期2012
