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

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

Author information

1
AFFiRiS AG, Vienna Biocenter, Vienna, Austria.
2
Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA.
3
Division of Neuroscience and Laboratory of Neurogenetics, National Institute on Aging, NIH, Bethesda, MD, USA.
4
Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA; Division of Neuroscience and Laboratory of Neurogenetics, National Institute on Aging, NIH, Bethesda, MD, USA; Department of Pathology, University of California, San Diego, La Jolla, CA, USA.
5
Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA; VA San Diego Healthcare System, La Jolla, CA, USA. Electronic address: rrissman@ucsd.edu.

Abstract

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

PMID:
31378574
DOI:
10.1016/j.jalz.2019.02.002

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