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Open Access 01-11-2018 | Original Paper

Region-specific depletion of synaptic mitochondria in the brains of patients with Alzheimer’s disease

Authors: Eleanor K. Pickett, Jamie Rose, Caoimhe McCrory, Chris-Anne McKenzie, Declan King, Colin Smith, Thomas H. Gillingwater, Christopher M. Henstridge, Tara L. Spires-Jones

Published in: Acta Neuropathologica | Issue 5/2018

Abstract

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 to examine synapses and synaptic mitochondria in two cortical regions (BA41/42 and BA46) from eight AD and nine 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 fourfold 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 or synaptic mitochondrial dynamics may be altered in AD.

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Title: Region-specific depletion of synaptic mitochondria in the brains of patients with Alzheimer’s disease
Authors: Eleanor K. Pickett
Jamie Rose
Caoimhe McCrory
Chris-Anne McKenzie
Declan King
Colin Smith
Thomas H. Gillingwater
Christopher M. Henstridge
Tara L. Spires-Jones
Publication date: 01-11-2018
Publisher: Springer Berlin Heidelberg
Published in: Acta Neuropathologica / Issue 5/2018
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-018-1903-2

ACC 2024 Congress

Springer Medicine

Region-specific depletion of synaptic mitochondria in the brains of patients with Alzheimer’s disease

Abstract

ACC 2024 Congress

Springer Medicine

Abstract

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