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

Christine C. Guo, Rachel Tan, John R. Hodges, Xintao Hu, Saber Sami, Michael Hornberger

Research output: Contribution to journalArticlepeer-review

138 Citations (Scopus)
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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.
Original languageEnglish
Pages (from-to)1527-1538
Number of pages12
Issue number5
Early online date16 Feb 2016
Publication statusPublished - 1 May 2016


  • intrinsic connectivity
  • cerebellum
  • neurodegeneration
  • selective vulnerability

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