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  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Glutamatergic mechanisms have been investigated in postmortem brain samples from schizophrenics and controls. D-[3H]Aspartate binding to glutamate uptake sites was used as a marker for glutamatergic neurones, and [3H]kainate binding for a subclass of postsynaptic glutamate receptors. There were highly significant increases in the binding of both ligands to membranes from orbital frontal cortex on both the left and right sides of schizophrenic brains. The changes are unlikely to be due to antemortem neuroleptic drug treatment, because no similar changes were recorded in other areas. A predicted left-sided reduction in D-[3H]aspartate binding was refuted at 5% probability, but not at 10%. Previously reported high concentrations of dopamine in left amygdala were strongly associated with low concentrations of D-[3H]aspartate binding in left polar temporal cortex in the schizophrenics. The findings are compatible with an overabundant glutamatergic innervation of orbital frontal cortex in schizophrenia. The results also suggest that schizophrenia may involve left-sided abnormalities in the relationship between temporal glutamatergic and dopaminergic projections to amygdala.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 777 (1996), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Notes: All individuals with Down's syndrome (trisomy 21-DS) develop the pathogenic hallmarks of Alzheimer's disease in old age (+40 years).1-4 The extent of pathology is variable, but it has been shown that the amount of β-amyloid pathology is variable and related to age and the degree of dementia.3 Thus, in DS, growing old is associated with a progressive pathological process which results in cognitive decline. However, neuropsychological studies of older DS subjects have identified a clinical dementia in only a proportion of cases.1-4These contradictory observations could be reconciled if some factor existed which modulated the rate and amount of β-amyloid pathology. Recent studies demonstrate an association between the apolipoprotein E4 (ApoE4) allele and the earlier age of onset in both sporadic8-9 and familial10 AD. Increased amounts of βamyloid pathology can also be related to the E4 allele. However, at present there are no data documenting the effects of ApoE genotype on the expression or degree of clinical symptoms of the disease. We have examined the ApoE genotype in a cohort of clinically evaluated elderly patients with DS in order to examine the effects of ApoE genotype on the clinical symptoms of dementia. We report here that, despite the presence of an active disease process, the ApoE E2 allele is associated with longevity and preservation of cognitive functioning.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1573-6830
    Keywords: head injury ; β-APP metabolism ; β-amyloid ; apolipoprotein E
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract 1. Alzheimer's disease is a heterogeneous disorder that may be caused by genetic or environmental factors or by a combination of both. Abnormalities in chromosomes 1, 14, and 21 have all been implicated in the pathogenesis of the early-onset form of the disease, while the ε4 allele of the apolipoprotein E gene (on chromosome 19) is now recognized as a risk factor for early- and late-onset sporadic and familial Alzheimer's disease. 2. The best-established environmental trigger for the disease is a head injury, based on epidemiological and neuropathological evidence. Approximately 30% of patients who die after a single episode of severe head injury show intracerebral deposition of β-amyloid protein (Aβ), a protein that is thought to be central to the pathogenesis of Alzheimer's disease. 3. Recent studies have revealed an over-representation of the apoE ε4 allele in those head-injured patients displaying Aβ pathology, thus providing the first evidence for a link between a genetic susceptibility (apoE ε4) and an environmental trigger (head injury) in the development of Alzheimer-type pathology.
    Type of Medium: Electronic Resource
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