Dementia of the Alzheimer Type: Clinical Genetics, Natural History, and Associated Conditions
01 Oct 1981-Archives of General Psychiatry (American Medical Association)-Vol. 38, Iss: 10, pp 1085-1090
TL;DR: Relatives of 125 probands, who had dementia of the Alzheimer type as proved by autopsy, were subjects of a genetic investigation and exhibited an excess of dementing illness consistent with genetic transmission.
Abstract: • Relatives of 125 probands, who had dementia of the Alzheimer type as proved by autopsy, were subjects of a genetic investigation. The relatives exhibited an excess of dementing illness consistent with genetic transmission. Risk to relatives decreased sharply as severity of the proband's illness decreased. Also, when compared with a control group and the general population, the relatives had excesses of Down's syndrome, lymphoma, and immune diatheses. These associated conditions also were more likely to be present when the proband had severe illness. Mortality at all ages was increased among the relatives.
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TL;DR: Advances in neurotransmitter systems involved in the symptomatic manifestations of neurological and psychiatric disorders reflect a close interaction between experimental and clinical neuroscientists in which information derived from basic neurobiology is rapidly utilized to analyze disorders of the human brain.
Abstract: Great emphasis is being placed on identification of neurotransmitter systems involved in the symptomatic manifestations of neurological and psychiatric disorders. In the case of Alzheimer's disease, which now seems to be one of the most common causes of mental deterioration in the elderly, compelling evidence has been developed that acetylcholine-releasing neurons, whose cell bodies lie in the basal forebrain, selectively degenerate. These cholinergic neurons provide widespread innervation of the cerebral cortex and related structures and appear to play an important role in cognitive functions, especially memory. These advances reflect a close interaction between experimental and clinical neuroscientists in which information derived from basic neurobiology is rapidly utilized to analyze disorders of the human brain.
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Cites background from "Dementia of the Alzheimer Type: Cli..."
...However, in 1981, Heston et al. first reported that relatives of 125 subjects who had autopsy-confirmed AD exhibited a significant excess of dementing illness consistent with genetic transmission (Heston et al., 1981)....
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TL;DR: Overexpression of the gene in brain tissue from fetuses with Down syndrome (trisomy 21) can be explained by dosage since the locus encoding the beta protein maps to chromosome 21.
Abstract: The amyloid beta protein has been identified as an important component of both cerebrovascular amyloid and amyloid plaques of Alzheimer9s disease and Down syndrome. A complementary DNA for the beta protein suggests that it derives from a larger protein expressed in a variety of tissues. Overexpression of the gene in brain tissue from fetuses with Down syndrome (trisomy 21) can be explained by dosage since the locus encoding the beta protein maps to chromosome 21. Regional localization of this gene by both physical and genetic mapping places it in the vicinity of the genetic defect causing the inherited form of Alzheimer9s disease.
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TL;DR: The chromosomal location of this defective gene has been discovered by using genetic linkage to DNA markers on chromosome 21 and provides an explanation for the occurrence of Alzheimer's disease-like pathology in Down syndrome.
Abstract: Alzheimer's disease is a leading cause of morbidity and mortality among the elderly. Several families have been described in which Alzheimer's disease is caused by an autosomal dominant gene defect. The chromosomal location of this defective gene has been discovered by using genetic linkage to DNA markers on chromosome 21. The localization on chromosome 21 provides an explanation for the occurrence of Alzheimer's disease-like pathology in Down syndrome. Isolation and characterization of the gene at this locus may yield new insights into the nature of the defect causing familial Alzheimer's disease and possibly, into the etiology of all forms of Alzheimer's disease.
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References
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Book•
01 Jan 1971
TL;DR: This book is a sound and diverse exposition of the subject of dementia and despite the numbers of contributors there is very little repetition.
365 citations
TL;DR: These studies showed that the "twisted tubule" which makes up the neurofibrillary tangle in many pathological situations is a bifilar helix made up of 130 A filaments.
354 citations
TL;DR: Although presenile dementia of Down's syndrome is ill-defined clinically, the marked histologic changes are so predictably age-related that this condition offers many insights into sequences of aging and degeneration in the human brain.
Abstract: Light and electron microscopic features in the presenile dementia that occurred in a 54 year old woman with Down9s syndrome were identical to those of Alzheimer9s presenile dementia. In both diseases, senile plaques and Alzheimer9s neurofibrillary tangles fill the cerebral cortex and are scattered through subcortical and brainstem nuclei. Although presenile dementia of Down9s syndrome is ill-defined clinically, the marked histologic changes are so predictably age-related that this condition offers many insights into sequences of aging and degeneration in the human brain.
216 citations
01 Jan 1952
186 citations
TL;DR: The Mortality from Leukaemia and Other Cancers Among Patients with Down's Syndrome * (Mongols) and Among their Parents and among their Parents is studied.
Abstract: The Mortality from Leukaemia and Other Cancers Among Patients with Down's Syndrome * (Mongols) and Among their Parents
154 citations