2. Academic Validation
  3. Nanoplastics trigger glial-neuronal collagen signaling miscommunication to exacerbate cognitive impairment in Alzheimer's disease

Nanoplastics trigger glial-neuronal collagen signaling miscommunication to exacerbate cognitive impairment in Alzheimer's disease

  • Alzheimers Dement. 2026 Jan;22(1):e71096. doi: 10.1002/alz.71096.
Yizhou Zhong 1 2,  Bingchi Fan 1,  Xiaohong Yang 1,  Yuji Huang 1 2,  Boxuan Liang 1,  Zhiming Li 1,  Xiaohu Ren 3,  Hongyi Xian 1 2,  Yanhong Deng 1,  Yu Feng 1,  Ruobing Bai 1,  Xiyun Huang 1,  Xiaoqing Chen 1,  Hao Li 1,  Shiyue Tang 1,  Lichun Ma 1,  Chen Yang 3,  Jianjun Liu 3,  Xifei Yang 3,  Xingfen Yang 1,  Zhenlie Huang 1 2 4
Affiliations

Affiliations

  • 1 National Medical Products Administration (NMPA) Key Laboratory for Safety Evaluation of Cosmetics, Guangdong Provincial Key Laboratory of Tropical Disease Research, Department of Toxicology, School of Public Health, Southern Medical University, Guangzhou, China.
  • 2 Department of Cardiovascular Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
  • 3 Shenzhen Key Laboratory of Modern Toxicology, Shenzhen Medical Key Discipline of Health Toxicology, Shenzhen Center for Disease Control and Prevention, Shenzhen, China.
  • 4 Guangzhou Key Laboratory of Forensic Multi-Omics for Precision Identification, School of Forensic Medicine, Southern Medical University, Guangzhou, China.
PMID: 41566532 DOI: 10.1002/alz.71096
Abstract

Introduction: Alzheimer's disease (AD) is a progressive neurodegenerative disorder with limited treatments and poorly defined environmental risks. Micro- and nanoplastics (MNPs) are widespread pollutants linked to neurotoxicity, but their role in AD remains unclear.

Methods: We investigated the effects of 90-day intragastric exposure to polystyrene nanoplastics (PS-NPs) in amyloid precursor protein/presenilin 1 (APP/PS1) mice using behavioral tests, brain imaging, histopathology, and cell-type-resolved proteomics.

Results: PS-NPs exacerbated cognitive deficits and hippocampal damage in APP/PS1 mice. Proteomic and CellChat analyses revealed PS-NPs enhanced neuroglial communication through the collagen-integrin axis. In vitro triculture demonstrated that PS-NPs strengthened collagen-mediated astrocyte-microglia-neuron signaling, whereas in vivo blockade with TC-I 15 suppressed Collagen activation and improved cognition in PS-NP-exposed APP/PS1 mice. Single-nucleus RNA Sequencing of human AD brains validated conserved activation of Collagen signaling.

Discussion: Our findings highlight that PS-NPs exacerbate cognitive impairment in AD by driving collagen-dependent neuroglial dysfunction, establishing MNPs as modifiable environmental risk factors.

Highlights: MNPs act as environmental risk factors that worsen cognitive impairment in AD. PS-NPs trigger glial-neuronal communication via the collagen-integrin axis in AD. PS-NP-induced astrocyte- and microglia-derived Collagen, driving neurotoxicity in AD. TC-I 15 blocked Collagen signaling and rescued cognition in PS-NP-exposed AD mice. Collagen signaling was upregulated in human AD brains, confirming disease relevance.

Keywords

Alzheimer's disease; aging‐related dementias; cellular communication; extracellular matrix; micro‐ and nanoplastics.

Figures
Products