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

Alzheimers Dement. 2019 Sep;15(9):1133-1148. doi: 10.1016/j.jalz.2019.02.002. Epub 2019 Aug 1.


Introduction: Immunotherapeutic approaches targeting amyloid β (Aβ) protein and tau in Alzheimer's disease and α-synuclein (α-syn) in Parkinson's disease are being developed for treating dementia with Lewy bodies. However, it is unknown if single or combined immunotherapies targeting Aβ and/or α-syn may be effective.

Methods: Amyloid precursor protein/α-syn tg mice were immunized with AFFITOPEs® (AFF) peptides specific to Aβ (AD02) or α-syn (PD-AFF1) and the combination.

Results: AD02 more effectively reduced Aβ and pTau burden; however, the combination exhibited some additive effects. Both AD02 and PD-AFF1 effectively reduced α-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 Aβ and/or α-syn may be of potential interest for the treatment of dementia with Lewy bodies.

Keywords: AFFITOPE®; Alzheimer's disease; Dementia with Lewy bodies; Immunization; Immunotherapy; α-synuclein.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alzheimer Disease
  • Amyloid beta-Peptides / immunology*
  • Animals
  • Humans
  • Immunologic Factors
  • Immunotherapy*
  • Lewy Body Disease / immunology*
  • Mice
  • Parkinson Disease
  • alpha-Synuclein / immunology*


  • Amyloid beta-Peptides
  • Immunologic Factors
  • alpha-Synuclein