Morphologically distinct plaque types differentially affect dendritic structure and organisation in the early and late stages of Alzheimer's disease

Abstract.

We have investigated the effects of the deposition of insoluble β-amyloid plaques on dendritic morphology within the neocortex. Labelling for β-amyloid identified three morphologically distinct plaque types present both within the brains of preclinical Alzheimer's disease (AD) and end-stage AD cases. In both preclinical and end-stage AD, the percentage area occupied by diffuse plaques contained a greater density of labelling for microtubule-associated protein-2 (MAP2) relative to the surrounding neuropil (case type, ratio of MAP2 labelling in plaque to MAP2 labelling in surrounding neuropil ± SEM: preclinical, 1.27±0.04; end-stage, 1.32±0.05). In contrast, there was a greater density of MAP2-labelled processes surrounding dense-cored plaques compared to that found within the plaque area (preclinical, 0.73±0.05; end-stage, 0.62±0.07). Fibrillar plaques demonstrated a transition from the early to late stages of AD, with a substantial decrease in the density of MAP2 labelling within the plaque area in end-stage AD cases relative to preclinical AD cases (preclinical, 1.01±0.1; end-stage, 0.72±0.05). The morphology of dendrites associated with dense-core or fibrillar plaques suggest physical disruption of the neuropil by β-amyloid plaque formation. These data demonstrate that plaque isoforms differentially affect dendritic morphology in both the early and late stages of AD, with progression to clinical AD associated with evolving dendritic damage localised to fibrillar and dense-core plaques.