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P2‐094: INTERLEUKIN‐1α AS PLEIOTROPIC BIOMARKER FOR NEUROINFLAMMATION IN ALZHEIMER'S DISEASE
Author(s) -
Mitrasinovic Olivera,
Kablar Nataša
Publication year - 2019
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.2019.06.2501
Subject(s) - neuroinflammation , normalization (sociology) , neuroprotection , proinflammatory cytokine , computational biology , biomarker , disease , database normalization , computer science , bioinformatics , inflammation , biology , neuroscience , immunology , medicine , artificial intelligence , genetics , pattern recognition (psychology) , sociology , anthropology
TRE promoter (Tag mice). Tag mice were paired with Camk2a-tTA transgenic mice (Off mice) and maintained on doxycycline (dox) diet. The offspring were maintained on dox diet until 30 days of age, at which point they were continuously maintained on standard diet. Tag mice were used as SV40T transgene controls. Animals were examined at 2, 4, 6, and 12 months of age. Vibratome sectioned brains were immunofluorescent labeled for Iba1, CD45, CD68, MHCII and GFAP. Cellular senescence was assessed using anti-p16 antibody. Results:Microglia and astrocyte activations are observed as early as 2 months of age after neuronal cell cycle activation. Tag/Off mice demonstrated increase in GFAP immunolabeling compared to Tag mice, indicative of astrocyte activation. Tag/Off mice also showed increased Iba1 immunostaining compared to Tag mice. A subset of Iba1-positive microglia showed co-labeling with CD45, CD68, or MHCII antibodies, demonstrating activated microglia. At 12-months of age, microglia demonstrates blebbing and p16 immunopositivity, both hallmarks of senescent phenotype. Conclusions:Our Tag/Off mice demonstrate early and persistent activation of microglia and astrocytes. Additionally, these mice develop senescent microglia phenotype along with Ab and tau pathologies following chronic and persistent neuronal cell cycle activation. Our mice simultaneously display the major pathological features of AD in the absence of APP or tau mutations, and thereby may represent a sporadic AD mouse model.