Cerebellar pathology in Alzheimer's disease.

Alzheimer's disease (AD) is one of the main causes of dementia in the western world. It is clinically characterized by memory impairment, deterioration of intellectual faculties and loss of professional skills. AD brains exhibit significant atrophy, predominantly in the temporal and parietal lobes, while light microscopy reveals deposition of senile plaques and neurofibrillary degeneration initially in the entorhinal cortex, the hippocampus, and in the acoustic and visual cortices, in the frontal lobe and the cerebellum in the advanced stages. Dendritic and spinal pathology, as well as loss of synapses are also key neuropathological features. The cerebellum is a critical part in the distributed neural circuits participating not only in motor function but also in autonomic, limbic and cognitive behaviours. Lesions of the motor cerebellum, mostly in lobules III-V in the anterior lobe and the secondary sensorimotor region in lobule VIII result in dysmetria of movement, however 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 lobule IX, are followed by dysmetria in the realms of intellect and emotion. Cerebellar functional topography has been demonstrated by tract tracing studies in non-human primates and in physiological and behavioural studies in rodents, cats and monkeys. Further studies revealed the existence of a mosaic of intrinsic connectivity networks that match the topographically precise cerebrocerebellar connections, while topographic organization of cerebellum is also evident in task-based functional MRI in healthy controls, and in clinical neurology, neuropsychology and neuropsychiatry studies in patients with cerebellar lesions. Although the cerebellum has not been extensively studied in AD, recent studies have revealed evidence of a unique pathological pattern of the cerebellar cortex, including loss of Purkinje cells, synaptic alterations in the mossy fibres, granule cell dendrites, parallel fibres and Purkinje cell dendrites with substantial loss of dendritic spines, and considerable alterations in ultrathin sections.