Effects of single and combined immunotherapy approach targeting amyloid β protein and α-synuclein in a dementia with Lewy bodies-like model

Introduction: Immunotherapeutic approaches targeting amyloid beta (A beta) protein and tau in Alzheimer's disease and alpha-synuclein (alpha-syn) in Parkinson's disease are being developed for treating dementia with Lewy bodies. However, it is unknown if single or combined immunotherapies targeting A beta and/or alpha-syn may be effective. Methods: Amyloid precursor protein/alpha-syn tg mice were immunized with AFFITOPEs (R) (AFF) peptides specific to A beta (AD02) or alpha-syn (PD-AFF1) and the combination. Results: ADO2 more effectively reduced A beta and pTau burden; however, the combination exhibited some additive effects. Both AD02 and PD-AFF1 effectively reduced alpha-syn, ameliorated degeneration of pyramidal neurons, and reduced neuroinflammation. PD-AFF1 more effectively ameliorated cholinergic and dopaminergic fiber loss; the combined immunization displayed additive effects. AD02 more effectively improved buried pellet test behavior, whereas PD-AFF1 more effectively improved horizontal beam test; the combined immunization displayed additive effects. Discussion: Specific active immunotherapy targeting A beta and/or alpha-syn may be of potential interest for the treatment of dementia with Lewy bodies. (C) 2019 Published by Elsevier Inc. on behalf of the Alzheimer's Association.