Summary

Lewy bodies are neuronal cytoskeletal inclusions that contain ubiquitin and neurofilament proteins. Lewy bodies are found in a wide range of clinical settings, ranging from clinically normal people to those with various extrapyramidal movement disorders to those with a progressive dementia. There is a rough correlation between the number and distribution of Lewy bodies and the degree of cognitive impairment. People with numerous and widespread Lewy bodies are inevitably demented. The frequency of both Lewy bodies and senile changes of the Alzheimer type increase in frequency with age, and not surprisingly coexist in some patients. This has lead to controversy as to whether Lewy body disease (LBD) may actually be a variant of Alzheimer's disease (AD). It is our working hypothesis, on the other hand, that the two disorders are independent, and that when AD pathology is present in LBD, it represents an independent disease process. Qualitative differences in cytoskeletal pathology in LBD and AD associated with senile plaques and in certain regions of the limbic lobe support this hypothesis. Specific molecular markers for LBD do not currently exist, but recent studies suggest that frequency of apolipoprotein E e4 allele may be increased in Lewy body disorders with coexistent AD, but apparently not in LBD without AD type pathology.

Neuropathology of aging

Insights from prospective clinicopathological studies

Prior to the 1980s there was a paucity of hard scientific information about the pathological correlates of cognitive changes that accompany normal aging. Most of the pathological studies prior to that time were based on small case studies or retrospective analyses for which longitudinal quantitative neuropsychological data were usually not available.