Premium
P2‐115: RAPAMYCIN TREATMENT INCREASES CEREBRAL BLOOD FLOW AND GUT MICROBIOME DIVERSITY IN EFAD MICE
Author(s) -
Parikh Ishita,
Ma David W.,
Hoffman Jared D.,
Wang Amy,
Thalman Scott,
Green Stefan J.,
Lin Ai-Ling
Publication year - 2018
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.2018.06.801
Subject(s) - microbiome , cerebral blood flow , neurovascular bundle , biology , genetically modified mouse , medicine , pathology , transgene , bioinformatics , gene , genetics
negatively correlated with the AD neuropathology.Methods:To understand the mechanism by which the TTC3 alteration may be acting to contribute to LOAD risk, induced pluripotent stem cells (iPSC) lines were developed to examine cellular consequences in neuronal cells, which can otherwise only be collected postmortem. Peripheral blood mononuclear cells (PBMCs) were extracted from the whole blood of three LOAD individuals bearing the p.S1038C change, as well as three age and ethnically matched control individuals. iPSC reprogramming was performed using Sendai virus. Results: Each iPSC line generated was validated for pluripotency through immunocytochemical staining and shown to be negative for any large-scale chromosomal abnormalities via karyotyping. These iPSC lines are being differentiated into cortical neurons by viral transduction of Neurogenin 2 to promote rapid maturation. There is evidence that modulation of TTC3 affects neurite growth (Berto, et al, 2007); therefore, morphological measures of axon and synapse formation will be assessed in differentiating neuronal cultures using live cell imaging. Alzheimer-specific phenotypes such as the levels of secreted beta amyloid and intercellular whole and phosphorylated tau will also be measured. Conclusions:Utilizing patient-specific iPSC lines carrying a segregating alteration in TTC3 will enable us to determine how this genetic alteration which may contribute to AD specific cellular phenotypes and, on a broader scale, LOAD risk.