O-glycosylation in sprouting neurons in Alzheimer disease, indicating reactive plasticity

Reactive plasticity, including axonal and dendritic sprouting and reactive synaptogenesis. has been proposed to contribute to the pathogenesis of seve ral neurological disorders. This work was aimed at identifying the possible role of protein glycosylation in the brain from patients with Alzheimer di sease (AD), using lectin histochemistry, as determinants of reactive plasti city. Results indicate an increase in the production of cryptic O-glycosidi cally linked proteins (NeuAc alpha2,6 Gal beta1,3GalNA alpha1.0 Ser/Thr or sialyl-T-antigen) in neuritic sprouting in AD brains as determined by posit ive labeling with Amaranthus leucocarpus (ALL, T-antigen-specific) and Macr obrachium rosenbergii (MRL, specific for NeuAc5,9Ac(2)) lectins. Immunohist ochemistry indicated that lectin staining was specific for the synaptic spr outing process (megancurites) in AD. These results were confirmed using ant i-synaptophysin and anti-GAP 43 antibodies, which recognized megancurites a nd dystrophic neurites around amyloid-beta deposits. In normal control brai ns, labeling with the aforementioned lectins was restricted to microvessels . Control experiments with neurarninidase-treated brain samples revealed po sitivity to the lectin front Arachis hypogaea (PNA), which is specific fur galactose. Our results suggest specific O-glycosylation patterns of protein s closely related to neuronal plasticity in AD.