Event Title

The Role of AMPH1 During Tau-mediated Neuroinflammation

Location

Hager-Lubbers Exhibition Hall

Start Date

19-4-2016 3:30 PM

Description

PURPOSE: Tauopathies such as Alzheimer’s disease are characterized by tau protein accumulation leading to neurodegeneration. Increasing evidence suggests a role of neuroinflammation in tauopathies, but the underlying mechanisms of inflammation remain poorly understood. Amphiphysin-1 (AMPH1) is a neuronal protein that has been associated with neurological disorders such as Alzheimer’s disease and Stiff Person Syndrome, suggesting AMPH1 could be involved in these two tauopathies. Recently, anti-AMPH1 anti-bodies were detected in serum of the tauopathy mouse model JNPL3 and a decrease in AMPH1 protein was associated with specific brain regions with tau pathology. We hypothesize that tau induces AMPH1 degradation in the brain and AMPH1 peptides activate microglia to induce gliosis leading to an autoimmune response. SUBJECTS: Two microglial immortalized cell lines EOC 13.31 and SIM-A1 were used. EOC 13.31 microglia possesses a dysfunctional TLR4 receptor while SIM-A1 expresses a normal TLR4 receptor. METHODS AND MATERIALS: SIM-A1 and EOC.13.31 treated with recombinant AMPH1 cleaved by calpain to generate AMPH1 peptide fragments. Control cells were treated with Lipopolysaccharides (LPS). Immunofluorescence techniques were used to assess markers of microglial activation. ANALYSIS: Comparative analysis of immunofluorescence bands. RESULTS: We show that AMPH1 peptides activate microglia in culture using a cell line expressing TLR4 receptor. CONCLUSIONS: Our results corroborate that tau pathology induces AMPH1 degradation, leading to AMPH1 peptides that elicit a neuroinflammation and systemic immune response.

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Apr 19th, 3:30 PM

The Role of AMPH1 During Tau-mediated Neuroinflammation

Hager-Lubbers Exhibition Hall

PURPOSE: Tauopathies such as Alzheimer’s disease are characterized by tau protein accumulation leading to neurodegeneration. Increasing evidence suggests a role of neuroinflammation in tauopathies, but the underlying mechanisms of inflammation remain poorly understood. Amphiphysin-1 (AMPH1) is a neuronal protein that has been associated with neurological disorders such as Alzheimer’s disease and Stiff Person Syndrome, suggesting AMPH1 could be involved in these two tauopathies. Recently, anti-AMPH1 anti-bodies were detected in serum of the tauopathy mouse model JNPL3 and a decrease in AMPH1 protein was associated with specific brain regions with tau pathology. We hypothesize that tau induces AMPH1 degradation in the brain and AMPH1 peptides activate microglia to induce gliosis leading to an autoimmune response. SUBJECTS: Two microglial immortalized cell lines EOC 13.31 and SIM-A1 were used. EOC 13.31 microglia possesses a dysfunctional TLR4 receptor while SIM-A1 expresses a normal TLR4 receptor. METHODS AND MATERIALS: SIM-A1 and EOC.13.31 treated with recombinant AMPH1 cleaved by calpain to generate AMPH1 peptide fragments. Control cells were treated with Lipopolysaccharides (LPS). Immunofluorescence techniques were used to assess markers of microglial activation. ANALYSIS: Comparative analysis of immunofluorescence bands. RESULTS: We show that AMPH1 peptides activate microglia in culture using a cell line expressing TLR4 receptor. CONCLUSIONS: Our results corroborate that tau pathology induces AMPH1 degradation, leading to AMPH1 peptides that elicit a neuroinflammation and systemic immune response.