Fibrillar amyloid-beta affects neurofibrillary changes but only in neuronsalready involved in neurofibrillary degeneration

The aim of this study of the cerebral cortex of 8 non-demented elderly subj ects and of 17 subjects in the severe stage of Alzheimer's disease (AD) (Gl obal Deterioration Scale stage 7/Functional Assessment Staging procedure st age 7a-f) was to examine the relationships between amyloid-beta (A beta) de posits and neurofibrillary degeneration. The study shows that neuronal proc esses with neurofibrillary changes are detectable in only a minority of fib rillar plaques: from 31% to 49% of fibrillar plaques within frontal, tempor al, parietal, limbic, occipital, and insular cortices. The correlations obs erved between the numerical densities of neurons with neurofibrillary tangl es (NFTs) and the densities of Thioflavin-S-positive fibrillar plaques with neurofibrillary changes (r=0.61; P<0.01) indicate that neurofibrillary pat hology in neocortical plaques reflects the topography and rate of neurofibr illary changes in neocortical neurons. The accumulation of abnormally phosp horylated tau in only some plaques indicates that fibrillar A<beta> enhance s paired helical filament accumulation locally only in dystrophic neurites already involved in neurofibrillary degeneration. The lack of correlation b etween the number of neurons with neurofibrillary changes and the number of all Thioflavin-S-positive fibrillar plaques (with and without neurofibrill ary changes) suggests that beta -amyloidosis does not contribute to initiat ion of neurofibrillary degeneration in neurons.