No abstract

Alzheimer's disease (AD) is the most common neurodegenerative disease characterized by neuronal loss due to amyloid beta (Aβ) aggregations, neurofibrillary tangles, and prominent neuroinflammation. Inflammatory processes in AD primarily occur in response to misfolded and aggregated proteins, or mislocalized nucleic acids and reactive microglia. Prolonged chronic neuroinflammation is thought to reinforce neuronal cell dysfunction and cell death. In our previous study we demonstrated that the interference with the pro-inflammatory mediator C5a by AFF1 vaccine at an early stage of disease is able to reduce microglia activation and amyloid plaque burden which is accompanied by ameliorated memory deficiency in Tg2576 mice, a mouse model of AD. In a follow-up study we tested the effect of a combinatorial vaccine targeting neuroinflammation by C5a and Aβ aggregates, two detrimental processes in AD. The amyloid plaque burden in the brain of Tg2576 mice was significantly reduced upon vaccination by the monovalent anti-C5a (AFF1) as well as anti-Aβ (AD02) vaccine, however, the combinatorial AFF1/AD02 vaccine showed a clear additive beneficial effect. Moreover, contextual memory in Tg2576 mice was significantly improved by the combinatorial AFF1/AD02 vaccine when compared to monovalent or control vaccines. Thus, targeting two neuropathological processes such as neuroinflammation and Aβ aggregation may represent a new and promising approach for the treatment of AD.