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However, the labelling (M + 4) in metabolites produced after direct metabolism of [U- 13 C] glutamate such as fumarate, malate and aspartate was significantly decreased in FTD3 neurons compared to isogenic controls (with the exception of fumarate and -kg M + 4 in H150, Fig 3 c 25 ), in contrast to the first turn TCA cycle in which metabolites were unmodified in FTD3 neurons compared with isogenic controls

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10.1186/s13045-020-00986-z 151

Prolonged oxidative and nitrosative damage to these membranes, lipids, and proteins, as is the case in AD and its earlier stage amnestic MCI, leads to synaptic dysfunctions and eventual synaptic loss, which underlies the most telling characteristic of this devastating dementing disorder: cognitive diminution (236)