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Causes and Consequences of Disturbances of Cerebral Glucose Metabolism in Sporadic Alzheimer Disease: Therapeutic Implications

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Book cover Frontiers in Clinical Neuroscience

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 541))

Abstract

Nosologically, Alzheimer disease (AD) is no one single disorder. Evidence is provided that a small proportion of 5% to 10% of all Alzheimer cases is caused by missense mutations in presenilin 1 or 2 genes on chromosomes 14 and 1, or in APP gene on chromosome 21 leading to autosomal dominant familial AD with early onset. This difference of inheritance serves as the basis of the amyloid cascade hypothesis which is limited to the above mutations. The latter hypothesis explains the increased formation of the APP derivative βA4 which aggregates to amyloid (Hardy and Selkoe, 2002). However, in constrast, the great majority of all Alzheimer cases (95% to 90%) was found to be sporadic in origin and of late onset. βA4 has not been proven to be necessary for the generation and the development of this neurodegenerative disorder (Joseph et al., 2001). Thus, the amyloid cascade hypothesis may not be accepted for sporadic Alzheimer disease (SAD). Instead, susceptibility genes may contribute to the onset of the latter type of AD. Best known are allelic abnormalities on the APOE-gene on chromosome 19 responsible for both anticipated onset and increase in severity of both inherited and sporadic AD. Candidate susceptibility genes for SAD are assumed to be on chromosomes 4, 6, 10 and 20 (Bertram et al., 2000a; Pericak-Vance et al., 2000). Other candidate genes did not show any association or linkage with AD (Bertram et al., 2000b).

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  1. Department of Pathochemistry and General Neurochemistry, University of Heidelberg, Im Neuenheimer Feld 220/221, Heidelberg, 69120, Germany

    Siegfried Hoyer

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    László Vécsei

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Hoyer, S. (2004). Causes and Consequences of Disturbances of Cerebral Glucose Metabolism in Sporadic Alzheimer Disease: Therapeutic Implications. In: Vécsei, L. (eds) Frontiers in Clinical Neuroscience. Advances in Experimental Medicine and Biology, vol 541. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-8969-7_8

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