There is an increasing amount of experimental and pathological evidence that protein misfolding and aggregation are critical elements in neurodegenerative diseases. Several groups have identified superoxide dismutase SOD1) as one of the proteins that may have a causative function in neurodegenerative diseases of CNS such as Alzheimer's (AD), amyotrophic lateral sclerosis (ALS), and Parkinson's (PD) forming misfolded protein aggregates as well as increasing oxidative damage in the misfolded state. We have postulated that disease specific epitopes (DSE) are uniquely exposed on misfolded SOD1 and may therefore be exploited as diagnostic and therapeutic targets. Early studies on transgenic mouse models for ALS have demonstrated the validity of this approach and some therapeutic benefits have been observed with both antibody-based and peptide-vaccine therapies. We now propose to extend this proof-of-principle to the treatment of AD.