The Cerebellum in Alzheimer's Disease

Abstract

The cerebellum is a relatively neglected area of the Alzheimer''s disease (AD) brain, probably because it was formerly thought to be spared by the disease. However, a number of pathological changes have now been revealed in the AD cerebellum, principally by immunocytochemical studies, including widespread deposits of diffuse amyloid, ubiquitin-immunoreactive dystrophic neurites, and increased microglia, but tau-immunoreactive neurofibrillary tangles have not been seen. Although the observed changes may be merely epiphenomenal to the pathological processes occurring in the AD neocortex and hippocampus, the morphological and immunocytochemical differences between AD cerebral cortex and cerebellar cortex may nonetheless give insights into the molecular factors involved in the development of the neuro-pathological lesions of AD brain.

Cerebellar Amyloid-β Plaques: How Frequent Are They, and Do They Influence 18F-Florbetaben SUV Ratios?

“…One explanation for our finding is that the signal from any potential 18 F-florbetaben binding in the cerebellum will be small, is likely to fall within the margins of error in PET signal measurement, and will therefore not be detectable. Another possible explanation may be the morphologic and immunocytochemical differences between the neuropathologic lesions of AD in the cerebral cortex and cerebellum (11). As expected, the amount of cerebellar Ab deposition assessed pathologically correlated positively with cortical SUVRs in the full sample of patients; subjects without Ab deposition in the cerebral cortex did not show Ab deposition in the cerebellum, and the higher the amount of cerebellar Ab deposition was, the higher was the cerebral cortical SUVR.…”

Alterations in Glucose Metabolism Induce Hypothermia Leading to Tau Hyperphosphorylation through Differential Inhibition of Kinase and Phosphatase Activities: Implications for Alzheimer's Disease

“…Last, we found that abnormal tau hyperphosphorylation occurred in the cerebral cortex and hippocampus but to a lesser extent in the cerebellum. In AD, NFTs are observed in the hippocampus and neocortex but not the cerebellum (Larner, 1997).…”

“…Interestingly, the cerebellum is not affected by reduced metabolism and is devoid of NFTs (Kushner et al, 1987;Larner, 1997). From these evidences, we hypothesized that in vivo alterations in glucose metabolism might be a potential cause of tau hyperphosphorylation.…”

Insulin Resistance, Cognitive Impairment and Neurodegeneration: Roles of Nitrosamine Exposure, Diet and Lifestyles

“…Cerebellar granule neurons are a suitable model because the cells are non-transformed, they can be efficiently transfected with non-viral vectors, and they are highly dependent upon insulin and IGF signaling for function. In addition, the cerebellar cortex is a target of neurodegeneration in various diseases including, AD (Cole, Neal et al 1993;Ishii, Sasaki et al 1997;Larner 1997;Wegiel, Wisniewski et al 1999). Gaithersburg, MD).…”