Cerebellum in Alzheimer's disease and frontotemporal dementia: not a silent bystander.

Abstract

This scientific commentary refers to ‘Network-selective vulnerability of the human cerebellum to Alzheimer’s disease and frontotemporal dementia’ by Guo et al. (doi: 10.1093/brain/aww003) The network theory of neurodegeneration builds upon the Hebbian notion that neurons that fire together wire together. In this vein, they also die together. Interconnected neural networks in the non-human primate were identified initially with physiological and lesion-degeneration techniques, and refined through anatomical tract tracing studies. Interconnected networks are now identified in the human brain through resting state functional connectivity MRI, and intrinsic connectivity networks have been defined that bind distributed neural hubs according to putative functional relevance (Fox et al. , 2005). At the mechanistic level, it has been proposed that neurodegeneration occurs within these interconnected networks as a result of self-propagating/prion-like spread of neurotoxic agents along neural pathways linking distributed nodes into functional modules (Prusiner, 2013). In this issue of Brain , Guo and co-workers provide evidence that network-based degeneration in Alzheimer's disease and frontotemporal dementia also extends to the cerebellum (Guo et al. , 2016). The cerebellum is a critical node in the distributed neural circuits subserving not only motor function but also autonomic, limbic and cognitive behaviours. Dysmetria of movement that characterizes the cerebellar motor syndrome results from lesions of the motor cerebellum, mostly in lobules III–V in the anterior lobe and the secondary sensorimotor region in lobule VIII. Dysmetria of thought in the realms of intellect and emotion (Schmahmann, 1991, 1996) manifests as the cerebellar cognitive affective syndrome (Schmahmann and Sherman, 1998), which occurs following lesions of the cognitive and limbic cerebellum in the posterior lobe, represented in lobules VI, VIIA (including lobules VIIAf and VIIAt at the vermis, and crus I and crus II in the hemispheres) and VIIB, and possibly in lobule IX as well. The vestibular …