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

Eleanor Pickett, Jamie Rose, C McCrory, Chris-Anne McKenzie, Declan King, Colin Smith, Thomas Gillingwater, Christopher Henstridge, Tara Spires-Jones

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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.

Original languageEnglish
Pages (from-to)747-757
Number of pages11
JournalActa Neuropathologica
Volume136
Issue number5
DOIs
Publication statusPublished - 6 Sep 2018

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Alzheimer Disease
Mitochondria
Synapses
Brain
Presynaptic Terminals
Amyloid
Mitochondrial Dynamics
Multivesicular Bodies
Transmission Electron Microscopy

Cite this

Pickett, E., Rose, J., McCrory, C., McKenzie, C-A., King, D., Smith, C., ... Spires-Jones, T. (2018). Region-specific depletion of synaptic mitochondria in the brains of patients with Alzheimer’s disease. Acta Neuropathologica, 136(5), 747-757. https://doi.org/10.1007/s00401-018-1903-2
Pickett, Eleanor ; Rose, Jamie ; McCrory, C ; McKenzie, Chris-Anne ; King, Declan ; Smith, Colin ; Gillingwater, Thomas ; Henstridge, Christopher ; Spires-Jones, Tara. / Region-specific depletion of synaptic mitochondria in the brains of patients with Alzheimer’s disease. In: Acta Neuropathologica. 2018 ; Vol. 136, No. 5. pp. 747-757.
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Pickett, E, Rose, J, McCrory, C, McKenzie, C-A, King, D, Smith, C, Gillingwater, T, Henstridge, C & Spires-Jones, T 2018, 'Region-specific depletion of synaptic mitochondria in the brains of patients with Alzheimer’s disease', Acta Neuropathologica, vol. 136, no. 5, pp. 747-757. https://doi.org/10.1007/s00401-018-1903-2

Region-specific depletion of synaptic mitochondria in the brains of patients with Alzheimer’s disease. / Pickett, Eleanor; Rose, Jamie; McCrory, C; McKenzie, Chris-Anne; King, Declan; Smith, Colin; Gillingwater, Thomas; Henstridge, Christopher; Spires-Jones, Tara.

In: Acta Neuropathologica, Vol. 136, No. 5, 06.09.2018, p. 747-757.

Research output: Contribution to journalArticle

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AU - Pickett, Eleanor

AU - Rose, Jamie

AU - McCrory, C

AU - McKenzie, Chris-Anne

AU - King, Declan

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AU - Gillingwater, Thomas

AU - Henstridge, Christopher

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AB - 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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