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Published on: July 26, 2011

LPI alleviates Alzheimer's disease pathology via the GPR55 receptor

Wenjie Xu1, Jiaqi Cao2, Yibo Liu2

  • 1Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Laboratory for Clinical Medicine, Capital Medical University, Beijing, China; Department of Morphology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, China.

Neuroscience
|June 26, 2026
PubMed

Insights

Reduced lysophosphatidylinositol (LPI) levels are an early sign of Alzheimer's disease (AD). LPI treatment shows therapeutic potential by reducing amyloid-beta and improving cognitive function via the GPR55 pathway.

Area of Science:

  • Neuroscience
  • Metabolomics
  • Neurodegenerative Diseases

Background:

  • Lysophosphatidylinositol (LPI) is an endogenous agonist for G protein-coupled receptor 55 (GPR55).
  • The specific role of LPI in Alzheimer's disease (AD) pathogenesis is not well understood.
  • Altered lipid metabolism is increasingly implicated in neurodegenerative disorders.

Purpose of the Study:

  • To investigate the role of LPI in Alzheimer's disease.
  • To explore the therapeutic potential of targeting the LPI-GPR55 axis in AD models.

Main Methods:

  • Serum metabolomic profiling was conducted in 5xFAD transgenic mice and human cohorts.
  • Behavioral tests assessed learning and memory in AD models.
  • Histological analyses examined amyloid-beta deposition, microglial aggregation, and astrocyte proliferation.
  • Pharmacological interventions using GPR55 antagonists and agonists were employed.

Main Results:

  • Reduced levels of multiple LPI species were observed in 5xFAD mice before overt amyloid-beta (Aβ) pathology, a finding mirrored in human AD samples.
  • Exogenous LPI administration decreased cerebral Aβ deposition and improved cognitive performance.
  • LPI treatment mitigated microglial aggregation, astrocyte proliferation, and hippocampal oxidative stress.
  • The protective effects of LPI were dependent on GPR55 activation, as confirmed by antagonist and agonist studies.

Conclusions:

  • Decreased LPI represents an early metabolic vulnerability in AD pathogenesis, particularly in the 5xFAD mouse model.
  • The LPI-GPR55 signaling pathway is a promising therapeutic target for early intervention in Alzheimer's disease.
  • Restoring LPI levels or activating GPR55 may offer neuroprotective benefits in AD.
Keywords:
Alzheimer’s diseaseGPR55LPIMetabolomicsNeuroinflammationOxidative stress

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