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- W2799822509 abstract "OBJECTIVE: To determine whether microglial morphology is significantly altered by the presence of repeat-associated non-AUG (RAN) translated proteins in ALS.BACKGROUND: Microglia are known to play a critical role in non-cell autonomous neuronal death in ALS. Recent data have suggested patients with C9orf72 expansion have even greater alterations in microglial morphology than other ALS patients. The mechanism for this is unknown although similar alterations in microglia have been identified in other repeat expansion diseases (e.g., Huntington’s disease). Here, we examined the hypothesis that RAN proteins, which form p62-positive cytoplasmic aggregates in patients with C9orf72 expansion, lead to alterations in microglial morphology in ALS, independent of TDP-43 and other pathologies.DESIGN/METHODS: Cytoplasmic RAN proteins were detected in autopsy-derived cerebellar cortical tissue of 65 ALS patients using anti-p62 Lck ligand immunofluorescence. Microglial density was quantified by CD68 immunohistochemistry. Iba1 immunofluorescence images were used to calculate an automated measure of cell area (Image J) and these images were also given a semi-quantitative score. Non-parametric statistical testing was used to examine the relationship between microglial measures and the presence of RAN proteins, as well as site of disease onset, duration, and age.RESULTS: p62-positive inclusions were identified in 12 patients. These patients significantly differed from p62-negative patients with respect to disease duration (2.45 versus 3.4 years, p = 0.01), but did not differ with respect to either Iba1- or CD68-based measures of microglia. Microglial measures in cerebellum were also not associated with age, duration of disease, or site of onset.CONCLUSIONS: Heterogeneity of microglia is present in ALS cerebellar cortex but this is not associated with the presence of RAN proteins in cerebellar granule cells. However, microglial morphology does not imply functional status so further tissue-based studies are underway to examine microglial function in the setting of p62-positive RAN proteins and ALS. Disclosure: Dr. Cykowski has nothing to disclose. Dr. Powell has nothing to disclose. Dr. Appel has nothing to disclose. Dr. Chang has nothing to disclose. Dr. Appel has received research support from Neuraltus, Inc., and GlaxoSmithKline." @default.
- W2799822509 created "2018-05-17" @default.
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- W2799822509 date "2016-04-05" @default.
- W2799822509 modified "2023-09-23" @default.
- W2799822509 title "Microglial Morphology Is Not Altered by the Presence of RAN Proteins in the Cerebellar Cortex of ALS Patients (P6.228)" @default.
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