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J Rogers

Publications and source records attributed to J Rogers.

At least 613 records · Page 34Linked to original sources
PubMedDate not supplied

APP-695 transcript prevalence is selectively reduced during Alzheimer's disease in cortex and hippocampus but not in cerebellum.

We previously found a selective loss of the brain specific APP-695 transcript in Alzheimer's disease (AD) cortex, which results in a 2.5-fold increase in the APP-751/APP-695 transcript ratio in AD (9). Here we report a similar increase in APP-751/APP-695 mRNA ratio in AD hippocampus. However, the cerebellum had a 6-fold lower ratio, which does not change in AD. The APP-695 mRNA species is greatly decreased (3-4-fold) in mRNA from AD cortex and hippocampus, whereas the APP-751 mRNA species is essentially unchanged. Considering hippocampal neuron loss and cortical neuron loss and atrophy, the data presented may be compatible with increased APP-751 mRNA and decreased APP-695 mRNA prevalence in remaining neurons in AD. A possible relationship between a high APP-751/APP-695 ratio and amyloid pathology is discussed.

Adult↗
PubMedDate not supplied

Demonstrating immune-related antigens in Alzheimer's disease brain tissue.

Immune system associated markers have recently been reported in Alzheimer's disease (AD) brain. However, previous studies have not consistently revealed these antigens in the central nervous system. Immunohistochemistry of HLA-DR and other immune antigens (e.g., CD4+, IL-2R) in AD cortical tissue was compared using paraformaldehyde-fixed versus snap-frozen unfixed tissue. In addition, a free-floating immunohistochemistry method was contrasted with an on slide procedure. Even with an HLA-DR antibody known to work well on fixed tissue, unfixed tissue gave superior results. Free-floating immunohistochemistry also increased sensitivity. Where morphologic considerations are paramount, brief fixation with free-floating methods provides a reasonable alternative.

Alzheimer Disease↗
PubMedDate not supplied

Efficient experimental design in aging studies.

Aged animals for research are expensive, take time to develop, and require rigorous attention to husbandry. As such, it behooves the investigators who use aged animals to do so efficiently. Moreover, correlations of many variables with longevity, and increased heterogeneity with age tend to bias aging research toward negative results. Multiple age groups, longitudinal assays, necropsy, and multidisciplinary experiments are factors in efficient experimental design that may significantly enhance the statistical power and interpretability of aging studies.

Aging↗
PubMedDate not supplied

Neuroimmunology of Alzheimer's disease: a conference report.

A multidisciplinary group met under the auspices of the National Institute on Aging and the Dell Foundation at the Princess Resort in San Diego, CA on April 5-6, 1991. The meeting was organized by Dr. Caleb E. Finch, University of Southern California, Dr. Zaven Khachaturian, National Institute on Aging, Dr. William Markesbery, University of Kentucky, Dr. Patrick McGeer, University of British Columbia, and Dr. Joseph Rogers, Institute for Biogerontology Research, and covered recent data suggesting neuroimmune correlates of Alzheimer's disease (AD). These findings span many of the major immune system phenomena, from major histocompatibility complex (MHC) antigens through cytokines and the complement cascade and suggest that some facets of AD pathogenesis may be immune related.

Alzheimer Disease↗
PubMedDate not supplied

Expression of the protooncogene bcl-2 in Alzheimer's disease brain.

To investigate the role of the apopotosis-related protooncogene bcl-2 in Alzheimer's disease (AD), we compared levels of its protein product, designated Bcl-2, in AD and nondemented (ND) age-matched control neocortical samples. The 26 kD Bcl-2 protein is increased in expression by more than three-fold in AD compared to ND samples as detected by immunoblots. Immunohistochemical analyses give similar results. In AD patients Bcl-2 immunoreactivity is dense and profuse and appears to occur on reactive astrocytes, whereas Bcl-2 immunoreactivity of astrocytes in ND patients is light and sparse. Staining of both gray and white matter is observed but is most prominent in the latter. Increased expression of Bcl-2 by astrocytes may partially underlie their resistance to loss in AD. By contrast, neuronal Bcl-2 immunoreactivity is more sparse and equivocal, perhaps reflecting the vulnerability of this cell type to apoptotic mechanisms in AD. High levels of Bcl-2 in glial cells may aid in cell survival of reactive astrocytes resulting in either beneficial or deleterious effects on neuronal viability.

Aged↗
PubMedDate not supplied

Characterization of glial cultures from rapid autopsies of Alzheimer's and control patients.

We have developed isolated and mixed cultures of microglia, astrocytes, and oligodendrocytes from rapid (mean of 2 h 55 min) autopsies of nondemented elderly patients and patients with Alzheimer's disease, Parkinson's disease, and multiple sclerosis. Cultures were derived from both the corpus callosum (CC) and superior frontal gyrus (SFG). Cultured microglia phagocytosed latex beads, were reactive for Dil-acetylated low density lipoprotein, were immunoreactive for CD68 and major histocompatibility complex II markers, and were not immunoreactive for fibroblast, astrocyte, or oligodendrocyte markers. Cultured astrocytes included fibrous and protoplasmic types, were immunoreactive for GFAP, and were not immunoreactive for fibroblast, microglia, or oligodendrocyte markers. Cultured oligodendrocytes were poorly adherent, were slow to develop, were immunoreactive for galactocerebroside, and were not immunoreactive for fibroblast, microglia, or astrocyte markers. Because they are readily manipulated under controlled experimental conditions, and because they permit immediate access to individual cells and sets of cells from patients who have actually suffered the disease, these cultures may provide an important new tool for unravelling the etiology and pathogenesis of human CNS disorders.

Aged↗
PubMedDate not supplied

Inflammation and Alzheimer's disease pathogenesis.

Appreciation of the role that inflammatory mediators play in Alzheimer's disease (AD) pathogenesis continues to be hampered by two related misconceptions. The first is that to be pathogenically significant a neurodegenerative mechanism must be primary. The second is that inflammation merely occurs to clear the detritis of already existent pathology. The present review addresses these issues by showing that 1) inflammatory molecules and mechanisms are uniquely present or significantly elevated in the AD brain, 2) inflammation may be a necessary component of AD pathogenesis, 3) inflammation may be sufficient to cause AD neurodegeneration, and 4) retrospective and direct clinical trials suggest a therapeutic benefit of conventional antiinflammatory medications in slowing the progress or even delaying the onset of AD.

Alzheimer Disease↗
PubMedDate not supplied

Microglial chemotaxis, activation, and phagocytosis of amyloid beta-peptide as linked phenomena in Alzheimer's disease.

Microglia are widely held to play important pathophysiologic roles in Alzheimer's disease (AD). On exposure to amyloid beta peptide (A beta) they exhibit chemotactic, phagocytic, phenotypic and secretory responses consistent with scavenger cell activity in a localized inflammatory setting. Because AD microglial chemotaxis, phagocytosis, and secretory activity have common, tightly linked soluble intermediaries (e.g., cytokines, chemokines), cell surface intermediaries (e.g., receptors, opsonins), and stimuli (e.g., highly inert A beta deposits and exposed neurofibrilly tangles), the mechanisms for microglial clearance of A beta are necessarily coupled to localized inflammatory mechanisms that can be cytotoxic to nearby tissue. This presents a critical dilemma for strategies to remove A beta by enhancing micoglial activation--a dilemma that warrants substantial further investigation.

Alzheimer Disease↗
PubMedDate not supplied

Inflammation and Alzheimer's disease.

Inflammation clearly occurs in pathologically vulnerable regions of the Alzheimer's disease (AD) brain, and it does so with the full complexity of local peripheral inflammatory responses. In the periphery, degenerating tissue and the deposition of highly insoluble abnormal materials are classical stimulants of inflammation. Likewise, in the AD brain damaged neurons and neurites and highly insoluble amyloid beta peptide deposits and neurofibrillary tangles provide obvious stimuli for inflammation. Because these stimuli are discrete, microlocalized, and present from early preclinical to terminal stages of AD, local upregulation of complement, cytokines, acute phase reactants, and other inflammatory mediators is also discrete, microlocalized, and chronic. Cumulated over many years, direct and bystander damage from AD inflammatory mechanisms is likely to significantly exacerbate the very pathogenic processes that gave rise to it. Thus, animal models and clinical studies, although still in their infancy, strongly suggest that AD inflammation significantly contributes to AD pathogenesis. By better understanding AD inflammatory and immunoregulatory processes, it should be possible to develop anti-inflammatory approaches that may not cure AD but will likely help slow the progression or delay the onset of this devastating disorder.

Alzheimer Disease↗
PubMedDate not supplied

Modeling microglial activation in Alzheimer's disease with human postmortem microglial cultures.

Alzheimer's disease (AD) is a uniquely human disorder. Despite intense research, the lack of availability of model systems has hindered AD studies though in recent years transgenic mouse models have been produced, which develop AD-like amyloid beta peptide (Abeta) plaques. For the study of inflammatory changes in AD brains, these transgenic mice may have limitations due to differences in the innate immune system of humans and rodents. Many studies of inflammatory processes in AD have focused on the role of activated microglia. Over the last 8 years, our research has focused on the properties of human microglia cultured from brain tissues of AD and non-demented (ND) individuals. As these are the cells observed to be activated in AD tissues, they represent a useful system for modeling the inflammatory components of AD. In this review, we summarize data by our group and others on the use of microglia for AD-related inflammatory research, with emphasis on results using human postmortem brain microglia. A range of products have been shown to be produced by human postmortem microglia, both constitutively and in response to treatment with Abeta, including proinflammatory cytokines such as interleukin (IL)-1beta, IL-6, tumor necrosis factor (TNF) alpha, and macrophage colony stimulating factor (M-CSF), along with complement proteins, especially C1q, superoxide radicals and neurotoxic factors. In our studies, we have demonstrated that there was a significant difference between AD and ND microglia in terms of their secretion of M-CSF and C1q. We also discuss the role of putative Abeta microglial receptors, particular recent data showing a role for the receptor for advanced glycation endproducts (RAGE) in mediating the responses of human microglia to Abeta. Finally, our studies on the use of an Abeta spot paradigm to model microglia interactions with plaques demonstrated that many of the features of AD inflammation can be modeled with postmortem brain derived microglia.

Alzheimer Disease↗
PubMedDate not supplied

Expression of immune system-associated antigens by cells of the human central nervous system: relationship to the pathology of Alzheimer's disease.

HLA-DR is a class II major histocompatibility complex antigen which in the periphery confers antigen presenting capability. We have previously shown that this marker is profusely expressed in cortex of elderly and Alzheimer's disease (AD) patients, as is the receptor for the lymphokine interleukin-2. We now report presence of additional immune-related antigens in AD, and distributional differences from normal elderly controls. In gray matter, HLA-DR immunoreactivity is normally sparse, except in AD where it co-localizes with virtually all neuritic plaques. HLA-DR positive T cells can be demonstrated in Alzheimer's disease brain tissue, as can instances of apposition between putative brain microglia and T cells. In addition, cells with the morphologic characteristics of astrocytes label for natural killer cell antigen (Leu-11), and apparent lymphocytes bearing T helper and T cytotoxic/suppressor cell antigens are observed. These and other data suggest that the glial proliferation and scavenger activity characteristic of Alzheimer's disease may occur in an immune context and may play an important role in the pathogenesis of the disorder.

Adolescent↗
PubMedDate not supplied

The neurophysiology of aging: insights from new applications of old techniques.

There is a regrettable paucity of data on the neurophysiology of aging, particularly single unit electrophysiologic research. The present paper is a commentary on reviews of the work of three groups of investigators who have played a lead role in developing electrophysiologic correlates of brain aging.

Aging↗
PubMedDate not supplied

Immunologic and tissue culture approaches to the neurobiology of aging.

The neurobiology of aging continues to attract scientists and techniques from the more fundamental disciplines, as witness the great strides now being made from molecular genetic approaches to Alzheimer's disease. The present report is a commentary on reviews of immune mechanisms and tissue culture methods applied to investigations of aging and age-related cognitive dysfunction.

Aging↗
PubMedDate not supplied

Molecular and cellular characterization of the membrane attack complex, C5b-9, in Alzheimer's disease.

The membrane attack complex, C5b-9, is of considerable importance in many inflammatory reactions. It is the terminal, cytolytic component of both classical and alternative pathway activation, and its presence presupposes other potentially destructive complement constituents, including anaphylotoxins and opsonins. We have characterized C5b-9 and its C9 constituent in the Alzheimer's disease (AD) and nondemented elderly (ND) brain using immunohistochemistry at the light and electron microscopic levels, Western blot analysis, and the reverse transcriptase polymerase chain reaction. We have also conducted in vitro ELISA assays of amyloid beta-peptide-stimulated SC5b-9 production. C5b-9 is abundantly present in Alzheimer's disease cortex, associated with neurofibrillary tangle containing neurons, dystrophic neurites within neuritic plaques, and neuropil threads, but is weakly detected, if at all, in nondemented elderly cortex under the same conditions. Staining of Alzheimer's disease sections is abolished both by deletion of primary antibody or preabsorption with purified SC5b-9.

Alzheimer Disease↗
PubMedDate not supplied

Metabolic disposition of pyrithiones.

The urinary pattern of pyrithione metabolites in urine of the rat, rabbit and rhesus monkey was similar to that of the swine after iv. administration of sodium pyrithione (Sodium Omadine) and the magnesium sulfate adduct of 2,2'-dithio-bis(pyridine-1-oxide), (Omadine MDS). The major metabolite accounting for 80% or more of the metabolites in urine was the S-glucuronide of 2-mercaptopyridine-N-oxide. After Omadine MDS administration, three transient metabolites and one persistent metabolite were observed in the plasma. The transient metabolites were tentatively identified as 2-methylthiopyridine-N-oxide, 2-methylsulfinylpyridine and 2-methylsulfinylpyridine-N-oxide. 2-Methylsulfonylpyridine was the only metabolite observed in the plasma 16 hr after Omadine administration. This metabolite could be detected 14 days after rats were treated repeatedly with a shampoo formulation containing Omadine MDS.

Administration, Topical↗