Spires-Jones, Tara. (2018). Region-specific depletion of synaptic mitochondria in the brains of patients with Alzheimer's disease - TEM data, [dataset]. University of Edinburgh. Medical School. Centre for Discovery Brain Sciences. http://dx.doi.org/10.7488/ds/2417.
Of all of the neuropathological changes observed in Alzheimer's disease (AD), the loss of synapses correlates most strongly with cognitive decline. The precise mechanisms of synapse degeneration in AD remain unclear, although strong evidence indicates that pathological forms of both amyloid beta and tau contribute to synaptic dysfunction and loss. Synaptic mitochondria play a potentially important role in synapse degeneration in AD. Many studies in model systems indicate that amyloid beta and tau both impair mitochondrial function and impair transport of mitochondria to synapses. To date, much less is known about whether synaptic mitochondria are affected in human AD brain. Here we used transmission electron microscopy (TEM) to examine synapses and synaptic mitochondria in two cortical regions (BA41/42 and BA46) from 8 AD and 9 control cases. In this study, we observed 3000 synapses and find region-specific differences in synaptic mitochondria in AD cases compared to controls. In BA41/42, we observe a four-fold reduction in the proportion of presynaptic terminals that contain multiple mitochondria profiles in AD. We also observe ultrastructural changes including abnormal mitochondrial morphology, the presence of multivesicular bodies in synapses, and reduced synapse apposition length near plaques in AD. Together, our data show region-specific changes in synaptic mitochondria in AD and support the idea that the transport of mitochondria to presynaptic terminals may be impaired in AD. This dataset includes all of the raw transmission electron micrographs used in the analysis.
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