Neocortical Variation of Aβ Load in Fully Expressed, Pure Alzheimer's Disease

The relationship between amyloid-beta (A beta) 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 A beta 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 A beta 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. A beta 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 A beta 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 A beta pathology.