Coexisting pathologies in the brain: influence of vascular disease and Parkinson's disease on Alzheimer's pathology in the hippocampus

The finding of more than one coexisting brain pathology in dementia suffere rs is not unusual. However, it is unclear how these different diseases may interact or influence the evolution of one another. In this study we analys e the hippocampal expression patterns of hyperphosphorylated tau, paired he lical filament (PHF)-related protein, beta-amyloid and synaptophysin in a g roup of Alzheimer's disease (AD) sufferers with and without additional path ology. Compared to cases with only AD-type pathology we found that the pres ence of additional vascular disease augmented the accumulation of hyperphos phorylated tau in the CA1 region of the hippocampus without affecting PHF f ormation in cases with mild AD changes and reduced the extent of PHF format ion in the CA2/3 and CA4 regions of the hippocampus in cases with severe AD pathology. We also found that synaptophysin immunoreactivity in the CA4 an d dentate gyrus in pure AD was inversely related to the extent of amyloid a ccumulation but not to neurofibrillary pathology in the same regions. These relationships were lost when additional pathology was present. Memory scor es obtained during life correlated closely with hyperphosphorylated tau and PHF-related protein expression in CA1 in pure AD but not in AD with additi onal pathology. Total amyloid and synaptophysin expression in the hippocamp us did not correlate with memory scores in any patient group. Our findings suggest that the interactions of two pathologies in the hippocampus are com plex and may differ depending on the stage reached in the evolution of a pr ogressive disease such as AD.