Neurochemical diversity of dystrophic neurites in the early and late stages of Alzheimer's disease

We examined the neurochemical and morphological diversity of abnormal neuri tes associated with P-amyloid plaque formation in the early and late stages of Alzheimer's disease. Preclinical Alzheimer's disease was characterised by the presence of abnormal neurites containing either neurofilament or chr omogranin A immunoreactivity. All clustered dystrophic neurites in these ca ses were associated with p-amyloid plaques. Neurofilament immunoreactive dy strophic neurites in preclinical Alzheimer's disease could be further subcl assified into bulb- and ring-like structures, and these abnormal neurites c ontained both phosphorylated and dephosphorylated neurofilament epitopes. D ystrophic neurites in Alzheimer's disease could be subdivided into predomin antly neurofilament, tau, or chromogranin A immunolabeled forms. Some neuro filament immunoreactive neurites had a core region labeled for tau. The neu rofilaments of the dystrophic neurites in Alzheimer's disease had the same complement of phosphorylation- and dephosphorylation-dependent epitopes as observed in preclinical cases. Therefore, an abnormal accumulation of varia bly phosphorylated neurofilaments represent the earliest cytoskeletal alter ation associated with dystrophic neurite formation. Furthermore, these data indicate that dystrophic neurites may "mature" through neurofilament-abund ant forms to the neurites containing the profoundly altered filaments label ed for tau. The precise morphological and neurochemical changes associated with dystrophic neurite formation suggests that P-amyloid plaques are causi ng physical damage to surrounding axons. The resultant axonal sprouting and profound cytoskeletal alterations would follow the chronic stimulation of the stereotypical reaction to such physical trauma. (C) 1999 Academic Press .