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Network-selective vulnerability of the human cerebellum to Alzheimer's disease and frontotemporal dementia.

Network-selective vulnerability of the human cerebellum to Alzheimer's disease and frontotemporal dementia.
Network-selective vulnerability of the human cerebellum to Alzheimer's disease and frontotemporal dementia.
Neurodegenerative diseases are associated with distinct and distributed patterns of atrophy in the cerebral cortex. Emerging evidence suggests that these atrophy patterns resemble intrinsic connectivity networks in the healthy brain, supporting the network-based degeneration framework where neuropathology spreads across connectivity networks. An intriguing yet untested possibility is that the cerebellar circuits, which share extensive connections with the cerebral cortex, could be selectively targeted by major neurodegenerative diseases. Here we examined the structural atrophy in the cerebellum across common types of neurodegenerative diseases, and characterized the functional connectivity patterns of these cerebellar atrophy regions. Our results showed that Alzheimer’s disease and frontotemporal dementia are associated with distinct and circumscribed atrophy in the cerebellum. These cerebellar atrophied regions share robust and selective intrinsic connectivity with the atrophied regions in the cerebral cortex. These findings for the first time demonstrated the selective vulnerability of the cerebellum to common neurodegenerative disease, extending the network-based degeneration framework to the cerebellum. Our work also has direct implications on the cerebellar contribution to the cognitive and affective processes that are compromised in neurodegeneration as well as the practice of using the cerebellum as reference region for ligand neuroimaging studies.
1527–1538
CC, Guo
85a02435-e391-4031-94ad-2e58bdfce659
Tan, R
d95992a7-805d-4ec7-8b3b-571c8c64706e
JR, Hodges
936bf0c6-b9ab-46eb-a3ed-2a6b719019aa
Hu, X
3cf32810-5cbb-4a6c-bfd0-05c95118e8b6
Sami, S
93469bbd-03c0-4c39-b1ab-af7ef22bfa47
Hornberger, M
a48c1c63-422a-4c11-9a51-c7be0aa3026d
CC, Guo
85a02435-e391-4031-94ad-2e58bdfce659
Tan, R
d95992a7-805d-4ec7-8b3b-571c8c64706e
JR, Hodges
936bf0c6-b9ab-46eb-a3ed-2a6b719019aa
Hu, X
3cf32810-5cbb-4a6c-bfd0-05c95118e8b6
Sami, S
93469bbd-03c0-4c39-b1ab-af7ef22bfa47
Hornberger, M
a48c1c63-422a-4c11-9a51-c7be0aa3026d

CC, Guo, Tan, R, JR, Hodges, Hu, X, Sami, S and Hornberger, M (2016) Network-selective vulnerability of the human cerebellum to Alzheimer's disease and frontotemporal dementia. Brain: a journal of neurology, 139 (5), 1527–1538. (doi:10.1093/brain/aww003).

Record type: Article

Abstract

Neurodegenerative diseases are associated with distinct and distributed patterns of atrophy in the cerebral cortex. Emerging evidence suggests that these atrophy patterns resemble intrinsic connectivity networks in the healthy brain, supporting the network-based degeneration framework where neuropathology spreads across connectivity networks. An intriguing yet untested possibility is that the cerebellar circuits, which share extensive connections with the cerebral cortex, could be selectively targeted by major neurodegenerative diseases. Here we examined the structural atrophy in the cerebellum across common types of neurodegenerative diseases, and characterized the functional connectivity patterns of these cerebellar atrophy regions. Our results showed that Alzheimer’s disease and frontotemporal dementia are associated with distinct and circumscribed atrophy in the cerebellum. These cerebellar atrophied regions share robust and selective intrinsic connectivity with the atrophied regions in the cerebral cortex. These findings for the first time demonstrated the selective vulnerability of the cerebellum to common neurodegenerative disease, extending the network-based degeneration framework to the cerebellum. Our work also has direct implications on the cerebellar contribution to the cognitive and affective processes that are compromised in neurodegeneration as well as the practice of using the cerebellum as reference region for ligand neuroimaging studies.

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More information

Accepted/In Press date: 6 December 2015
e-pub ahead of print date: 16 February 2016

Identifiers

Local EPrints ID: 505254
URI: http://eprints.soton.ac.uk/id/eprint/505254
PURE UUID: 8e5f863a-440b-441e-be5b-9220cc085645
ORCID for M Hornberger: ORCID iD orcid.org/0000-0002-2214-3788

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Date deposited: 02 Oct 2025 16:53
Last modified: 03 Oct 2025 02:18

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Contributors

Author: Guo CC
Author: R Tan
Author: Hodges JR
Author: X Hu
Author: S Sami
Author: M Hornberger ORCID iD

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