ISSN:1350-7540    

出版商:OVID    

年代:1995

数据来源: OVID

ISSN:1350-7540    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

We have summarized the literature on cognitive changes in normal aging. The concepts of normal aging, age-associated memory impairment, and their possible continuum with dementia are discussed. Epidemiologic, genetic, radiological, as well as neuropsychological and endocrine contributions to the understanding of cognition in the elderly, are reviewed.

ISSN:1350-7540    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Three genetic loci for Alzheimer's disease have been identified. These are the amyloid precursor gene on chromosome 21, a gene for early-onset autosomal dominant Alzheimer's disease on chromosome 14, and the risk-modifying geneAPOEon chromosome 19. Additional Alzheimer's disease genes remain to be found. The genes identified by studying inherited forms of Alzheimer's disease are now being used to understand the initiating steps in the pathogenesis of the disease.

ISSN:1350-7540    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

The presence of amyloid deposits in the parenchyma of the amygdala, hippocampus, and neocortex is a major histopathological hallmark of Alzheimer's disease. The principal component of amyloid is amyloid beta, a 39–43 amino acid peptide comprised of a portion of the transmembrane domain and the extracellular domain of the amyloid precursor proteins. Amyloid precursor proteins occur as several amyloid beta-containing isoforms of 695, 751, and 770 amino acids. In cultured cells, amyloid precursor proteins mature through the constitutive secretory pathway, and some cell-surface-bound amyloid precursor proteins are cleaved by an enzyme, designated as alpha-secretase, within the amyloid beta domain, an event that precludes amyloid beta amyloidogenesis. Two additional pathways of amyloid precursor protein processing include an endosomal/lysosomal pathway that generates a complex set of amyloid precursor protein-related membrane-bound fragments, some of which contain the entire amyloid beta sequence; and, by mechanisms not fully understood, secretion of amyloid beta 1–40 into the conditioned mediumin vitroand its presence in cerebrospinal fluidin vivo.The intracellular sites of enzymes responsible for proteolytic cleavage at the amino- and carboxyl-termini of amyloid beta, termed gamma- and beta-secretase, respectively, have not been identified. Molecular genetic investigations have identified a variety of mutations in the amyloid precursor protein gene that segregate with early-onset familial Alzheimer's disease and with hereditary cerebral hemorrhage with amyloid, Dutch type. Several of these mutations appear to influence amyloid precursor protein processing and result in the production of higher levels or longer amyloid beta-related peptides that are inherently more fibrillogenic. Although a variety of lines of evidence implicate amyloid precursor protein and amyloid beta in Alzheimer's disease, the mechanism(s) by which amyloid beta influences the biology and vulnerability of neural cells is not fully clear. Amyloid beta toxicity is being exploredin vitroandin vivo.Finally, recent progress has been made in the generation of transgenic mice expressing amyloid precursor protein or amyloid beta that recapitulate a subset of the pathology observed in Alzheimer's disease.

ISSN:1350-7540    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Therapeutic trials activity in Alzheimer's disease increased during the past year, with both the initiation of new and the continuation of ongoing symptomatic treatment studies designed to demonstrate enhancement of cognitive abilities. Interest in interventions for noncognitive or behavioral symptoms has also increased. Attempts to convert new basic scientific discoveries into clinical approaches that slow the progression of the disease also generated enthusiasm. Timely consideration of certain critical methodological, ethical, and policy issues are likely to enhance this late phase activity in drug development in the years to come.

ISSN:1350-7540    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Amyloidosis and prionosis are disorders of protein conformation. The general mechanisms involved in amyloidogenesis are reviewed here. Recent progress in the molecular pathogenesis of cerebral amyloids is illustrated by three genetic disorders: hereditary amyloid angiopathies of Icelandic and Dutch origins and Gerstmann-Straussler-Scheinker disease.

ISSN:1350-7540    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Major advances have been made in prion diseases. Recent data indicate that the prion protein is likely to be a synaptic protein with a functional role in synaptic transmission. An impressive body of evidence suggests that (1) the normal prion protein plays a central role in prion replication; (2) the replication process implies an interaction between the normal prion protein and the pathogenic prion protein; and (3) the pathogenic prion protein is the infectious agent, the infectivity of which is dependent on its abnormal conformation. Genetic and protein analyses have expanded the spectrum of prion diseases and have underlined the complexity of genotype-phenotype interactions.

ISSN:1350-7540    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

A subset of pedigrees with dominant inheritance of familial amyotrophic lateral sclerosis have mutations in superoxide dismutase 1. Initial studies suggested that disease-linked mutations impaired superoxide dismutase 1 activity, which is consistent with the notion that disease results from increased oxidative injury. However, results of recent cell culture and transgenic studies demonstrate that mutant proteins retaining high levels of superoxide dismutase 1 activity cause motor neuron degeneration; elevating the level of wild-type superoxide dismutase 1 does not cause disease. These findings suggest that the familial amyotrophic lateral sclerosis phenotype may occur through other mechanisms that can now be explored in model systems.

ISSN:1350-7540    

出版商:OVID    

年代:1995

数据来源: OVID

ISSN:1350-7540    

出版商:OVID    

年代:1995

数据来源: OVID