An anti-inflammatory neuroenhancer mitigates amyloid-β pathology to improve Alzheimer's disease therapy

TL;DR

A new treatment for Alzheimer's disease reduces brain plaques and inflammation, improving memory and cognition in mice.

Contribution

A novel neuroenhancer that simultaneously targets amyloid-β and neuroinflammation in Alzheimer's disease.

Findings

RB@LCP-AR reduces amyloid-β production and aggregation in Alzheimer's disease models.

The treatment alleviates neuroinflammation and restores memory and cognition in AD mice.

Rutin in the neuroenhancer protects neurons by reducing mitochondrial dysfunction and ROS.

Abstract

β-amyloid (Aβ) inhibition significantly attenuates the early-stage Alzheimer's disease (AD) progression, but the improvement in cognitive function remains limited by neuroinflammation. Here, we developed a bioinspired neuroenhancer that concurrently targets both Aβ aggregation and neuroinflammation. Rutin and small interfering RNA targeting beta-site amyloid precursor protein cleaving enzyme 1 (siBACE1) were co-loaded into the calcium phosphate core, which was further coated with lipid bilayers and Angiopep-2/rabies virus glycoprotein 29 peptides to form the multifunctional neuroenhancer (RB@LCP-AR). RB@LCP-AR not only releases siBACE1 to silence BACE1 expression and block Aβ production from the cleavage of amyloid precursor protein, but also releases Rutin to suppress the Aβ aggregation. Moreover, the released Rutin of RB@LCP-AR directly alleviates Aβ-induced mitochondria dysfunction and intracellular ROS production in neuronal cells. Notably, the targeting of RB@LCP-AR to neurons and the inhibition of Aβ reduce the microgliosis and astrogliosis, further alleviating neuroinflammation and synapse loss. Consequently, AD mice receiving RB@LCP-AR treatment efficiently recovered their memory and cognition. Our study thus provides a coordinated targeting of Aβ and neuroinflammation inhibition, holding considerable potential to promote the recovery of memory and cognition in AD.

A dual-functional bioinspired neuroenhancer RB@LCP-AR reduces amyloid-β burden and while eliminating neuroinflammation to rescue memory and cognition loss in Alzheimer's disease mice.Image 1

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