Neuropathological substrates of Alzheimer's disease and Parkinson's disease

Abstract

The pathology of Alzheimer's disease (AD) and Parkinson's disease (PD) is characterized by degeneration of certain vulnerable neuronal populations that display several types of cytoskeletal abnormalities (Alzheimer-type lesions and Lewy bodies, respectively). These may serve as diagnostic markers, although they can be found in both types of disorders and, less frequently, in brains of normal aged individuals. AD pathology shows a preponderance for hippocampal, neocortical, and forebrain cholinergic systems; the hallmark of PD is damage to the nigrostriatal dopaminergic system. Both disorders show frequent involvement of subcortical projection systems that can be similar in quality and distribution, with similar multiple neuromediator dysfunction. The results of morphometric studies of some subcortical nuclei in AD and PD are reported and related with neurochemical data. In addition to classical forms of AD and PD, both types of lesions can coexist suggesting an increased risk of PD in patients with AD and vice versa. The basis for an association between the two disorders is unknown. Many AD cases with signs of PD have additional PD pathology, while cortical Alzheimer lesions may be seen in demented PD patients. However, dementia in PD does not imply coexistent cortical AD pathology; prominent subcortical lesions alone, or in combination with cortical AD pathology, may occur. AD and PD may show some differences in the primary locus of degenerative changes in specific cortical and subcortical neuronal systems, but the causative factors, mutual relations, and relative contributions to the clinical syndromes remain to be elucidated.