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[P3–121]: ROLES OF ORNITHINE DECARBOXYLASE (ODC) IN REGULATION OF AMYLOID β‐INDUCED MICROGLIAL NEUROINFLAMMATION
Author(s) -
Lin ChihLi,
Huang ChienNing,
Li HsinHua,
Liu GuangYaw,
Hung HuiChih,
Lai TeJen
Publication year - 2017
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2017.06.1332
Subject(s) - neuroinflammation , microglia , ornithine decarboxylase , neurotoxicity , neurodegeneration , microbiology and biotechnology , biology , inflammation , chemistry , immunology , biochemistry , medicine , enzyme , toxicity , disease , organic chemistry
neurofibrillary tangles, and chronic neuroinflammation. The amyloid cascade hypothesis purports that AD pathogenesis is driven by Ab accumulation leading to neuronal death. Recent genome-wide association studies have shown that Triggering Receptor Expressed on Myeloid cells 2 (TREM2) is associated with risk for late onset AD. We have found that TREM2 protein expression is upregulated in LOAD patient brain lysates compared to aged-matched controls. We hypothesize that differential TREM2 expression by monocytes has a pathological role in LOAD progression. Methods: To explore this further, using cultured murine and human microglia, we developed a chronic stimulation model – overnight high dose Aß stimulation with subsequent low dose Aß stimulation. Results:Our data show that chronic Aß exposure reduces TREM2 protein expression, whereas in peripheral macrophages, chronic Aß increases TREM2 protein Expression. This pattern mirrors the inflammatory profile within these myeloid populations. Conclusions: We believe that the chronic expression of Aß perturbes the microglial immune response, creating a tolerized phenotype that may be seen in AD brains.