DataVXACS NanoPaper
journal article·2025-11-04

Modulating Amyloid Pathology–Neural Hyperexcitability Crosstalk for Alzheimer’s Disease Therapy

Ying Wang, Jinfu Li, Ding Zhang, Yinyao Feng, Mengni Zhou, Chang Zhou, Dijia Wang, Gaolin Qiu, Wei Dai, Zhilai Yang, Yunjiao Zhang, Li Zhang, Xuesheng Liu, Jiqian Zhang

ACS Nano· Volume 19· Issue 43
Publisher page
Source abstract

Abstract

Current therapies for Alzheimer’s disease (AD) primarily target amyloid-β (Aβ) pathology using monoclonal antibodies, yet their limited efficacy partly results from unintended exacerbation of neural hyperexcitability. This highlights a critical but under-appreciated link between Aβ clearance and neuronal network dysfunction. Here, we designed R@AClipo, a nanotherapeutic platform that codelivers the TREM2 agonist peptide COG1410 and the glutamate modulator riluzole via Angiopep-2–modified liposomes capable of crossing the blood–brain barrier. In AD model mice, R@AClipo upregulated TREM2 expression and enhanced microglial-mediated Aβ clearance. Concurrently, it reduced glutamate accumulation and mitigated neuronal hyperexcitability, as measured by in vivo fiber photometry. Notably, TREM2-driven Aβ clearance alone modestly reduced hyperexcitability, independent of riluzole, contrasting with the excitatory effects frequently associated with antibody-based Aβ therapies. This combinatorial strategy improved cognitive performance and restored neural activity patterns without observable toxicity. Together, these findings support a physiologically compatible strategy that targets the pathological crosstalk between Aβ accumulation and neural hyperexcitability, offering a promising avenue for AD intervention.
Source: openalex_inverted_index · Quality: baseline

Research context

Nanomaterials

OpenAlex topics: Functional Brain Connectivity Studies · Neural dynamics and brain function · Computational Drug Discovery Methods

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Anesthesiology, The First Affiliated Hospital of Anhui Medical University, Key Laboratory of Anesthesia and Perioperative Medicine of Anhui Higher Education Institutes

Anhui Medical University

Department of Anesthesiology

The First Affiliated Hospital of Anhui University of Chinese Medicine

Reproductive Medicine Center, Department of Obstetrics and Gynecology

The First Affiliated Hospital of Anhui Medical University

School of Medicine

South China University of Technology

National Engineering Research Center for Tissue Restoration and Reconstruction and Key Laboratory of Biomedical Engineering of Guangdong Province

Department of Urology

the First Affiliated Hospital of Anhui Medical University and Anhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation

Funding

Excellent Young Talents Fund Program of Higher Education Institutions of Anhui Province · National Natural Science Foundation of China · Anhui Provincial Postdoctoral Research Funding Program · Distinguished Young Scholar of Anhui Colleges · Outstanding Scientific Research and Innovation Team Program for Universities in Anhui Province · Health Research Program of Anhui · Science Foundation for Outstanding Young Scholar of Anhui Colleges

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