REVIEW article
Front. Cell. Neurosci.
Sec. Cellular Neuropathology
Volume 19 - 2025 | doi: 10.3389/fncel.2025.1705069
This article is part of the Research TopicAdvances in Explainable Analysis Methods for Cognitive and Computational NeuroscienceView all articles
Microglial TREM2 and Cognitive Impairment: Insights from Alzheimer's Disease with Implications for Spinal Cord Injury and AI-assisted Therapeutics
Provisionally accepted
- 1Department of Orthopaedics, Second Hospital of Anhui Medical University, Hefei, China
- 2Institute of Orthopaedics, Research Center for Translational Medicine, The Second Hospital of Anhui Medical University, Hefei 230601, China, Hefei, China
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Cognitive impairment is a frequent but underrecognized complication of neurodegenerative and traumatic central nervous system disorders. Although research on Alzheimer's disease (AD) revealed that microglial triggering receptor expressed on myeloid cells 2 (TREM2) plays a critical role in inhibiting neuroinflammation and improving cognition, its contribution to cognitive impairment following spinal cord injury (SCI) is unclear. Evidence from AD shows that TREM2 drives microglial activation, promotes pathological protein clearance, and disease-associated microglia (DAM) formation. SCI patients also experience declines in attention, memory, and other functions, yet the specific mechanism of these processes remains unclear. In SCI, microglia and TREM2 are involved in inflammation and repair, but their relationship with higher cognitive functions has not been systematically examined. We infer that TREM2 might connect injury-induced neuroinflammation in the SCI with cognitive deficits, providing a new treatment target. Artificial intelligence (AI) offers an opportunity to accelerate this endeavor by incorporating single-cell transcriptomics, neuroimaging, and clinical data for the identification of TREM2-related disorders, prediction of cognitive trajectories, and applications to precision medicine. Novel approaches or modalities of AI-driven drug discovery and personalized rehabilitation (e.g., VR, brain–computer interface) can more precisely steer these interventions. The interface between lessons learned from AD and SCI for generating new hypotheses and opportunities for translation.
Keywords: Alzheimer's disease, artificial intelligence, cognitive impairment, Microglia, spinal cord injury, TREM2
Received: 15 Sep 2025; Accepted: 14 Oct 2025.
Copyright: © 2025 Wu, Yu, Tian, Cheng and Jing. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Juehua Jing, jjh_hu@163.com
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