Dudas_2002_Neurobiol.Aging_23_97

High molecular weight glycosaminoglycans GAG and proteoglycans PG affect pathological changes of the brain in Alzheimer's disease AD PG stimulate the processing and aggregation of amyloid-beta Abeta protect the protein from proteolysis and increase the formation of neurofibrillary tangles by inducing the hyperphosphorylation of tau protein These effects may be competitively inhibited by GAG.We have studied the effects of orally by gavage and subcutaneously s.c administered low molecular weight heparin C3 4-10 oligosaccharides MW 2.1 kDa USP value 12 U/mg on abnormal tau-2 protein immunoreactivity in the rat hippocampus following a single unilateral intra-amygdaloid administration of Abeta(25-35 Oral administration of C3 25 mg/kg once daily was initiated 3 days prior to Abeta(25-35 administration and was continued daily for an additional 14 days S.c administration of C3 2.5 mg/kg twice daily was started 3 days prior to and was continued for 32 days after Abeta(25-35 administration Animal brains were subsequently processed for tau-2 ChAT-immunoreactivity choline acetyltransferase ChAT activity and acetylcholinesterase AChE activity Both oral and s.c administration of C3 attenuated Abeta(25-35 induced appearance of tau-2-immunoreactive IR perikarya in the ipsilateral hippocampus P 0.05 Hippocampal cholinergic enzyme activity in C3 treated animals was not significantly different from control animals.The present findings suggest that C3 might be used successfully to prevent abnormal tau protein formation in chronic neurologic diseases such as AD Moreover our data demonstrate that the mechanism of this effect does not appear to influence the cholinergic system of the brain