Neocortical variation of Abeta load in fully expressed, pure Alzheimer's disease.

The relationship between amyloid-beta (Abeta) deposition and tau-related neurofibrillary changes is a key issue in the pathogenesis of Alzheimer's disease (AD). The aim of this study was to investigate the extent and cortical distribution of Abeta and tau pathology, their mutual links and their correlation with the duration of the disease in thirty-nine patients with fully expressed AD. By tau immunohistochemistry, we identified different patterns of distribution of neurofibrillary changes that were ascribed to Braak stage V and VI. The disease duration was longer in patients at Braak stage VI than in those at V. Morphometric analysis carried out in several neocortical areas demonstrated that Abeta load was not uniform among individuals and also varied in the same patient throughout the neocortex, showing decreased severity from associative fields in the premotor and primary motor areas. Abeta load was higher at Braak stage VI than at stage V and correlated positively with disease duration in primary motor cortex and in superior temporal gyrus. Overall, we documented a marked heterogeneity in the extent of Abeta deposition even in AD brains at final stages of disease that cannot be completely explained by a simple, regular build up of this pathologic protein in the cerebral cortex during the course of the disease. This study may be relevant for the correct evaluation of therapeutic strategies for AD that specifically address Abeta pathology.