NR AWGJ
AU Hardy,J.
TI Genetic dissection of the etiologies and pathogeneses of Alzheimer's and Parkinson's diseases and related disorders
QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Oral sessions ORAL-42
PT Konferenz-Vortrag
AB Genetic analyses have implicated mutations in the APP gene as one cause of early onset, autosomal dominant, Alzheimer's disease. These mutations, like mutations in the presenilin genes, alter the amount of the peptide, A42 produced during APP processing. Genetic analysis of a recent genome screen for late onset Alzheimer's disease, has implicated the APP locus as risk factor locus, for late onset disease although frank mutations have not been found: this suggests that genetic variability in APP expression contributes to the risk of this form of the disorder: not surprising, perhaps, given the longstanding association between trisomy 21 and AD. Similarly, mutations in the tau gene cause autosomal dominant tangle disease (FTDP-17), and genetic variation at the tau locus, but not coding changes, is associated with the sporadic tangle diseases, progressive supranuclear palsy and corticobasal degeneration: this suggests that genetic variability in either tau expression or in tau splicing contributes to the risk of these diseases. Finally, mutations in the alpha-synuclein gene cause autosomal dominant Lewy body disease, and genetic variability (haplotypic association) at the synuclein locus contributes to sporadic disease: our recent demonstration that one cause of autosomal dominant disease is a triplication of the -synuclein locus, indicates that the most likely explanation of this observation is that this haplotypic association reflects the fact that genetic variability in the control of -synuclein contributes to disease risk. These observations have in common support for the notion that these common diseases are initiated by overexpression of key pathogenic proteins which are close to their threshold of solubility.
AD Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Building 10, Room 6C103, MSC1589, Bethesda, MD 20892, USA. E-mail: hardyj@mail.nih.gov
SP englisch
PO Italien