Progression of neurofibrillary changes and PHF-tau in end-stage Alzheimer's disease is different from plaque and cortical microglial pathology

In terminal Alzheimer's disease (AD) the frequency of plaques was found to be reduced in single cases. To test this finding in a larger sample, and in order to determine whether the number of plaques labeled with different ma rkers and the distribution of neurofibrillary tangles are correlated positi vely to each other and to the degree of dementia, a sample of 134 autopsy b rains with and 15 without AD-related pathology has been examined. All of th e cases were staged according to Braak and Braak. Both the frequency of pla ques immunopositive for beta-amyloid, amyloid precursor protein, and apolip oprotein E and that of microglial cells in the cortex and in the white matt er were determined semiquantitatively. The content and distribution of PHF- tau was ascertained by ELISA and immunohistochemistry. Both the clinical de mentia rating and the global deterioration scale were used as clinical para meters retrospectively. Correlation coefficients were calculated for all pa rameters and differences were evaluated statistically. With progressive dis tribution of neurofibrillary tangles and increasing content of PHF-tau, the plaque stages and the degree of cortical microglia reaction increased up t o the Braak-stages IV and V, thereafter showing a slightly decreasing tende ncy in the investigated regions. In end-stage AD resorption of P-amyloid se ems to surpass its deposition The microglial reaction in the white matter c orrelated neither with the Braak-stage nor with the accumulation of amyloid . With regard to the degree of dementia, both scales correlated well with t he pathological chan es. Our data show that neuronal cytoskeletal alteratio ns progressively increase with progressive dementia until the end stage of KD in contrast to the frequencies of plaques and cortical microglial cells, and are therefore preferable for staging purposes. (C) 1999 Elsevier Scien ce Inc.