Learn More
The amyloid beta protein is deposited in the brains of patients with Alzheimer's disease but its pathogenic role is unknown. In culture, the amyloid beta protein was neurotrophic to undifferentiated hippocampal neurons at low concentrations and neurotoxic to mature neurons at higher concentrations. In differentiated neurons, amyloid beta protein caused(More)
Microdialysis is a widely used in vivo sampling technique commonly used to monitor extracellular levels of a variety of molecules including neurotransmitters and metabolites. To facilitate interpretation of microdialysis results, this study critically examines changes in synaptic morphology induced by microdialysis. Tissue surrounding microdialysis probes(More)
Deposition of the beta-amyloid protein in senile plaques is a pathologic hallmark of Alzheimer disease (AD). Focal deposition of beta amyloid in the adult rat cerebral cortex caused profound neurodegenerative changes, including neuronal loss and degenerating neurons and neurites. Chronic induction of the Alz-50 antigen appeared in neurons around focal(More)
The role of growth factors in the pathogenesis of Alzheimer disease is unknown. The beta-amyloid protein accumulates abnormally in the brain in Alzheimer disease and is neurotoxic to differentiated hippocampal neurons in culture. Nerve growth factor (NGF) increased the neurotoxic potency of a beta-amyloid polypeptide by a factor of approximately 100,000,(More)
Neurofibrillary tangles (NFT) are the principal structural alteration of neuronal cell bodies in Alzheimer disease as well as in normal aging of the human brain. While the ultrastructure of these intraneuronal lesions has been extensively studied, the biochemical composition of the fibers comprising the NFT is unknown. We report the production of three(More)
As a comparison to previous analyses of purified amyloid plaque cores from Alzheimer's disease (AD) brain, we performed protein chemical and immunocytochemical studies on amyloid filaments extracted from meningeal blood vessels of patients with Alzheimer's disease. Results were compared with those obtained from identically prepared fractions of aged normals(More)
During aging of the human brain, and particularly in Alzheimer's disease, progressive neuronal loss is accompanied by the formation of highly stable intra- and extraneuronal protein fibers. Using fluorescence-activated particle sorting, a method has been developed for purifying essentially to homogeneity the extracellular amyloid fibers that form the cores(More)
An organotypic mouse brain slice culture system of Alzheimer's disease (AD) under low oxygen partial pressures was developed to determine the antioxidant properties of the pineal hormone melatonin in vitro. Assays for biochemical markers of oxidative stress including redox active iron assay, heme-oxygenase-1 and 8-hydroxyguanosine inmunoreactivity were(More)
A 3.3-kilobase DNA complementary to human microtubule-associated protein 2 (MAP2) was sequenced by the dideoxy method. The 3' end terminates at an internal EcoRI site before the polyA tail. Due to the arrangement of the cDNA insert in the lambda gt11 vector, the MAP2 fragment is not fused to beta-galactosidase when expressed. The Chou Fasman algorithm for(More)
To elucidate the relationship between amyloid fibril formation in Alzheimer disease (AD) and the primary structure of the beta-amyloid protein (beta-AP), we investigated the ability of peptides sharing sequences with beta-AP to form fibrils in vitro and to recognize anti-beta-amyloid antisera. The peptides, which were synthesized using a FMOC solid phase(More)