Aug 6, 2019

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

Alzheimer's & Dementia : the Journal of the Alzheimer's Association
Markus MandlerRobert A Rissman

Abstract

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. 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. 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. Specific active immunotherapy targeting Aβ and/or α-syn may be of potential interest for the treatment of dementia with Lewy bodies.

  • References95
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Citations

Mentioned in this Paper

Nerve Degeneration
Alzheimer's Disease
SNCA wt Allele
AFF1
Programmed Cell Death Protein 1
Amyloid
Administration @ Physiological Systems and Anatomical Regions @ Introduction @ Central Vein @ Open @ Immunotherapeutic
Tau Proteins
Pyramidal Cells
Inflammation

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