Amyloid-beta (Abeta) peptide pathology in Alzheimer's disease (AD) comprises extracellular plaques and cerebral amyloid angiopathy (CAA). In Parkinson's disease (PD), alpha-synuclein forms intraneuronal Lewy bodies (LBs), and cortical LBs are thought to play a major role in cognitive decline designated as PD with dementia. As there is increasing evidence that Abeta may also promote alpha-synuclein fibrillization, we assessed the relationship between LB pathology and Abeta deposition in 40 cases of PD and 20 age-matched controls. In five cortical areas, we established the severity of Abeta plaque load using an approach similar to that recommended by CERAD in AD. LB densities were determined using a morphometric approach. CAA was graded using previously described scales. The APOE genotype was established in 38 PD and 19 control cases. We have found that the overall Abeta plaque burden and, in particular, the diffuse plaque load shows a statistically significant 'large' correlation with the overall cortical LB burden. The strength of this correlation further increases in PD cases (about 50% of the cases) with moderate to high Abeta plaque load. The APOE epsilon4 allele is over-represented in this subgroup. Our data indicate a strong association between pathologically identifiable Abeta plaque burden and alpha-synuclein load in cerebral cortex and provide indirect evidence that Abeta pathology is likely to be an important factor contributing to cognitive decline in a subgroup of PD patients.
Observations were made with the electron microscope on biopsies from the frontal cerebral cortex of four patients showing the clinical symptoms of advanced Alzheimer's disease (AD). Sections from all four biopsies showed neuronal dendrites, and to a lesser extent, perikarya, packed with paired helical filaments (PHFs) and a correlated complete loss of the normal content of microtubules. It was usually impossible to visualize the beginning and end of the PHF since it passed out of the plane of section. However, not infrequently, PHFs could be seen apparently arising at or from the surfaces of cytomembranes. Such membranes (in perikarya or dendrite) often formed irregular stacks or lamellated bodies. These membranes were invariably agranular (i.e. not studded with ribosomes) and so might be considered as pathological forms of smooth endoplasmic reticulum (SER). A correlation is established between the known biochemical nature of PHFs and their postulated membrane origin.
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