AGGREGATION OF ALPHA-SYNUCLEIN IN LEWY BODIES OF SPORADIC PARKINSONS-DISEASE AND DEMENTIA WITH LEWY BODIES

Lewy bodies (LBs) are hallmark lesions of degenerating neurons in the brains of patients with Parkinson's disease (PD) and dementia with Lew y bodies (DLB). Recently, a point mutation in the gene encoding the pr esynaptic alpha-synuclein protein was identified in some autosomal-dom inantly inherited familial PD pedigrees, and light microscopic studies demonstrated alpha-synuclein immunoreactivity in LBs of sporadic PD a nd DLB. To characterize alpha-synuclein in LBs, we raised monoclonal a ntibodies (MAbs) to LBs purified from DLB brains and obtained a MAb sp ecific for alpha-synuclein that intensely labeled LBs. Light and elect ron microscopic immunocytochemical studies performed with this MAb as well as other antibodies to alpha- and beta-synuclein showed that alph a-synuclein, but not beta-synuclein, is a component of LBs in sporadic PD and DLB. Western blot analyses of highly purified LBs from DLB bra ins showed that full-length as well as partially truncated and insolub le aggregates of alpha-synuclein are deposited in LBs. Thus, these dat a strongly implicate alpha-synuclein in the formation of LBs and the s elective degeneration of neurons in sporadic PD and DLB.