Effect of soluble interleukin‐10 receptor expression in mouse models of Alzheimer's disease: Molecular and cell biology/neuroinflammation. (7th December 2020)

• Record Type: Journal Article
• Authors: Koller, Emily J.; De La Cruz, Elsa Gonzalez; Weinrich, Mary J.; Antezana, Gustavo; Ibanez, Kristen R.; Ryu, Daniel H.; Lewis, Jada; Chakrabarty, Paramita
• Is Part Of: Alzheimer's & dementia. Volume 16(2020)Supplement 2
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-12-07
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.041927
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: Alzheimer's disease (AD) is a neurodegenerative disease characterized pathologically by intracellular neurofibrillary tangles (NFT), extracellular amyloid β (Aβ) plaques, and neuroinflammation. Interleukin 10 (IL10) is an anti‐inflammatory cytokine released by immune and glial cells. Since IL10 is anti‐inflammatory, it has the potential to be a therapy for neurodegenerative diseases with an inflammatory component. However, contrary to what we expected, an earlier study from our group showed that overexpression of IL10 actually led to an increase in Aβ plaque burden in a mouse model of Aβ plaques. Therefore, we proposed to assess the effect of overexpression of the soluble extracellular portion of the IL10 receptor (sIL10R) on disease pathogenesis in both an Aβ mouse model and tau mouse models. The premise was that this soluble form of the receptor would attenuate IL10 signaling, thus reversing its anti‐inflammatory properties. Method: To investigate the effect of sIL10R expression on Aβ plaques, we used adeno‐associated virus (AAV) to express sIL10R in neonatal TgCRND8 mice and aged them 3 or 6 months. We next investigated whether sIL10R also affected tau pathology in two tau mouse models: a slowly‐progressing spinal cord tauopathy model (JNPL3) and a rapid model with primarily cortical and hippocampal tauopathy (rTg4510). Result: Assessment of Aβ plaque burden revealed decreased Aβ plaque load in the younger TgCRND8 cohort, but this effect was not observed in the 6 month old mice. We observed a significant reduction of phosphorylated tau and a trend towards reduced p62 levels in the JNPL3 mice. However, we did not observe changes in phosphorylated tau or p62 levels in 4 month old or 6 month old rTg4510 mice. Quantification of neuroinflammatory markers in APP and tau mouse models showed distinct patterns of neuroinflammation specific to each model. Conclusion: Our study demonstrates that a decoy receptor may be a potential therapeutic for Alzheimer's disease and that attenuation of Aβ and tau pathogenesis may occur at different rates and at different disease stages. Future experiments will center around characterizing possible mechanisms underlying these changes.