Affiliations: [a] Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy | [b] Department of Clinical Neurosciences, University of Palermo, Palermo, Italy | [c] DPSMC, University of Udine, Udine, Italy | [d] Indiana University School of Medicine, Indianapolis, IN, USA | Sanders-Brown Center on Aging and Alzheimer's Disease Center, Department of Chemistry, University of Kentucky, Lexington, Kentucky, USA
Abstract: The relationship between amyloid-β (Aβ) 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 Aβ 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 Aβ 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. Aβ 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 Aβ 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 Aβ pathology.
Keywords: Alzheimer's disease, amyloid-β burden, Braak staging, immunohistochemistry, morphometry, neurofibrillary tangles, senile plaques, tau protein
