A Novel Aβ B-cell epitope Vaccine, Aβ1-10 with carrier protein OVA and KLH reduce Aβ-induced neuroinflammation mediated neuropathology in mouse model of Alzheimer’s disease

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-beta (Aβ) plaque deposition and neurofibrillary tangles, which collectively drive neuroinflammation, synaptic dysfunction, and cognitive decline. Here, we investigated whether a peptide epitope vaccine targeting the Aβ1–10 sequence could mitigate Aβ-induced pathology in AD mouse model. Three Aβ1–10 peptides, i.e. Aβ1–10-N, Aβ1–10-D1H, and Aβ1–10-S8R were synthesized, and Aβ1–10-S8R was further conjugated to ovalbumin (OVA) or keyhole limpet hemocyanin (KLH) to enhance immunogenicity. Among seven treatment groups, Aβ1–10-D1H and Aβ1–10-S8R, particularly when conjugated to OVA or KLH, effectively suppressed Aβ, amyloid-beta precursor protein (APP), and beta-secretase 1 (BACE-1) expression, decreased inflammatory cytokine production by astrocytes and microglia, and increased the levels of key synaptic markers (synaptophysin, synaptosomal-associated protein 23 [SNAP-23], postsynaptic density protein 95 [PSD-95]). Carrier protein conjugation also elevated immunoglobulin G (IgG) levels in the spleen, indicative of a robust humoral response. Taken together, these findings demonstrate that Aβ1–10-based immunization, especially with OVA or KLH conjugation, reduces Aβ-driven neuroinflammation, synaptic dysfunction, and memory deficits, suggesting a promising immunotherapeutic strategy for AD.