Amyloid-β dimers bind to microglial TLR2 to induce early neuroinflammation and cognitive deficits in Alzheimer's disease.

Authors

Yifei Liu, Kaiwen Tian, Kun Jiao, Na Wu, Kunhe Ma, Lingyun Shang, Miaomiao Du, Yujia Wang, Xinyuan Wang, Jing Lu, Jing Zhang, Baian Chen

Published in

Neuroscience. Nov 10, 2026. Epub Nov 10, 2026.

Abstract

Previous studies have shown that amyloid-β (Aβ) oligomers are implicated in the pathogenesis of Alzheimer's disease (AD). Aβ oligomers include various molecules with distinct characteristics, such as dimers and trimers; among these, Aβ dimers have been found to possess neurotoxicity. This study found that Aβ dimers can induce microglial proliferation, enhanced phagocytosis, and pro-inflammatory polarization in the mouse brain even before cognitive impairment occurs, and this effect was validated in vitro using BV2 cells. Mechanistically, Aβ dimers bind to the microglial receptor TLR2, activating the downstream NF-κB signaling pathway and upregulating the expression of inflammatory factors. Knocking down TLR2 significantly reverses the Aβ dimer-induced inflammatory response and alleviates microglial-mediated neuronal damage. Furthermore, repeated intracerebral injections of Aβ dimers lead to impaired learning and memory in mice, as well as loss of hippocampal neurons and synapses; these changes are independent of amyloid plaque deposition and tau protein hyperphosphorylation. In summary, Aβ dimers induce early neuroinflammation and cognitive deficits by binding to TLR2 on microglia, providing a new molecular target for early intervention in AD.

PMID:
43009006
Bibliographic data and abstract were imported from PubMed on 11 Nov 2026.

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