Postmortem analysis of brains of patients with Alzheimer's disease (AD) has led to diverse theories about the causes of the pathology, suggesting that this complex disease involves multiple physiological changes. In an effort to better understand the variety and integration of these changes, we generated a gene expression profile for AD brain. Comparing affected and unaffected brain regions in nine controls and six AD cases, we showed that 118 of the 7050 sequences on a broadly representative cDNA microarray were differentially expressed in the amygdala and cingulate cortex, two regions affected early in the disease. The identity of these genes suggests the most prominent upregulated physiological correlates of pathology involve chronic inflammation, cell adhesion, cell proliferation, and protein synthesis (31 upregulated genes). Conversely, downregulated correlates of pathology involve signal transduction, energy metabolism, stress response, synaptic vesicle synthesis and function, calcium binding, and cytoskeleton (87 downregulated genes). The results support several separate theories of the causes of AD pathology, as well as add to the list of genes associated with AD. In addition, approximately 10 genes of unknown function were found to correlate with the pathology.
Glycosaminoglycans (GAGs) may be effective as a therapeutic strategy in the treatment of Alzheimer's Disease (AD). Previous work from this group using a rat model showed that a single intra-amygdaloid injection of A$(25-35) could induce abnormal tauimmunoreactive perikarya in the hippocampus. Furthermore, administration of the GAG C3, an ultra low molecular weight heparin mixture of 4-10 oligosaccharides (MW~2.1) could decrease A$(25-35) -induced tau-2 immunoreactivity in this model of AD.In this study, we evaluated the effects of stereotaxic intra-amygdaloid injection of A$(25-35) (5 nml/3:l) and of C3-treatment (administered subcutaneously, s.c.) on dendritic morphology of Golgi-impregnated CA1 pyramids of the hippocampus. Subjects were young-adult, male F344 rats.There were four groups:• the controls were rats with intra-amygdaloid (i-a) injection of vehicle (trifluoroacetic acid, TFA, 3 :l) followed by saline (32 days, s.c., 1 ml/kg, b.i.d.) (N = 10); • treatment groups consisted of:• i-a injection of A$ (5 nmol/3:l) followed by 32 days of saline (s.c., 1 ml/kg, b.i.d.)(N = 5); • i-a injection of A$ (5 nmol/3 :l) followed by GAG-treatment (32 days of C3, 2.5 mg/kg s.c., b.i.d.) (N = 5); and • i-a injection of vehicle (TFA, 3 :l) followed by the C3 GAG (32 days, 2.5 mg/kg s.c., b.i.d.) (N = 5).Formalin-fixed coronal blocks of rat frontoparietal cortex, which included the underlying hippocampus, were stained using the Rapid Golgi method. Slides were sectioned at 120 :m. All brains were coded, and 6 well-impregnated CA1 neurons were
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.