Bromelain prevents Alzheimer's disease progression by suppressing oxidative stress and upregulating apolipoprotein A1 in 5x familial Alzheimer's disease transgenic mice

Alzheimer's disease (AD), a devastating neurodegenerative disorder, is the most prevalent form of dementia. The pathological hallmark of AD is the accumulation of β-amyloid (Aβ) in the hippocampus and cerebral cortex, leading to oxidative stress, neuronal death, and brain atrophy. Bromelain, a proteolytic enzyme extracted from pineapple ( Ananas comosus ), exhibits potent antioxidant properties. This study investigated the therapeutic potential of bromelain on AD pathogenesis and its underlying molecular mechanisms using 5x familial AD (5xFAD) mice that carry five AD-linked mutations. Beginning at 10 weeks of age, mice were administered bromelain (20 mg/kg) or vehicle daily for 6 weeks. Bromelain treatment significantly improved motor function, spatial learning, and memory in 5xFAD mice. Analysis of brain tissues revealed reduced levels of Aβ precursor protein and Aβ protein in the hippocampus and cerebral cortex of bromelain-treated mice, potentially mediated through downregulation of ATP-binding cassette subfamily A member 5 and ATP-binding cassette subfamily B member 9 transporters and upregulation of apolipoprotein A1. Furthermore, bromelain demonstrated neuroprotective effects by attenuating oxidative stress and suppressing apoptotic pathways. These findings suggest that bromelain may represent a promising therapeutic strategy for AD and related dementia disorders. • Bromelain improves motor function, spatial learning, and memory in Alzheimer's disease (AD) mice. • Bromelain reduces β-amyloid by increasing apolipoprotein A1 in the brains of AD mice. • Bromelain increases antioxidant capacity by increasing the superoxide dismutases in the brains of AD mice. • Bromelain protects neurons by reducing cell death in the hippocampus and cortex of AD mice.