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Frontotemporal dementia (FTD) is a neurodegenerative disease that causes deterioration of the frontal and temporal lobe. Detection is pivotal in preventative care, but current screening methods are not sensitive enough to detect early-stage disease. Synapse loss has been implicated as

Frontotemporal dementia (FTD) is a neurodegenerative disease that causes deterioration of the frontal and temporal lobe. Detection is pivotal in preventative care, but current screening methods are not sensitive enough to detect early-stage disease. Synapse loss has been implicated as an early contributor to neurodegeneration and subsequent atrophy. Fluorine-18 fluorodeoxy-glucose (18[F]-FDG) positron emission tomography (PET) is a noninvasive imaging biomarker method frequently used as a surrogate measure for synaptic activity in the brain. PET scans using 18[F]-FDG tracers were performed on progranulin (GRN) knockout mice (Grn-/-), a commonly used mouse model of FTD. Interestingly, 18[F]-FDG PET at both, 9 months and 11 months, two time points considered early symptomatic in the Grn-/- mouse model, did not detect significant changes in synaptic activity, suggesting that no synapse loss has occurred yet at these early stages of FTD in this model. After the last PET scan, the imaging data were validated via fluorescent immunostaining for pre- and post-synaptic marker proteins SV2 and PSD95, respectively. Quantifications in several brain regions, including the frontal cortex, did not reveal any significant differences in protein expression, supporting the lack of aberrant 18[F]-FDG tracer uptake measured via PET. Additional examinations for activated microglia, a known aspect of FTD pathology recently observed in end Grn-/- mice, did not reveal microglia activation as measured via CD68 immunostaining. These data suggest that Grn-/- mice at 9 and 11 months do not exhibit synaptic dysfunction in the frontal cortex when measured via 18[F]-FDG PET or immunostaining of pre- and postsynaptic marker proteins SV2 and PSD95.
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    Title
    • Validation of Early Synapse Loss in a Mouse Model of Frontotemporal Dementia
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    Date Created
    2022
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    • Partial requirement for: M.S., Arizona State University, 2022
    • Field of study: Biology

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