A multi-targeting immunotherapy ameliorates multiple facets of Alzheimer's disease in 3xTg mice

Alzheimer's disease (AD) is an intricate disorder involving amyloid deposits, neurofibrillary tangles, and chronic neuroinflammation. Though current A beta-directed immunotherapies effectively eliminate amyloid plaques, their limited clinical benefits and notable safety concerns arise from overlooking two other neglected neurodegenerative features. Compelling evidence highlights synergistic cooperation between A beta and tau, underscoring the imperative need to develop combinational therapies to target the diverse pathologies of AD. In this study, we present a dual AD vaccine combining A beta and pTau vaccines, eliciting robust and enduring antibody responses against pathological A beta and pTau in 3xTg transgenic mice. It significantly eradicated A beta plaques and pTau tangles, suppressed neuroinflammatory factors, and markedly enhancing cognitive abilities in 3xTg mice. Mechanistically, peripheral antibodies penetrated the brain, recognizing and inhibiting A beta and pTau aggregation, thereby reducing their cytotoxicity. In summary, this innovative multi-targeting immunotherapy remarkably ameliorates diverse AD pathologies, demonstrating maximum benefits in slowing the clinical progression of AD.