Genetic Linkage Analysis in Early-Onset Familial Alzheimer’s Dementia
At least 50% of all patients with senile dementia are clinically diagnosed having Alzheimer’s disease (AD; Terry and Katzman 1983). At autopsy, AD is confirmed by the large abundance of senile plaques and neurofibrillary tangles in the brain, particularly in the hippocampus and cerebral cortex (Brun 1983). In as many as 40% of these AD patients there is strong evidence of a previous family history of the disease, indicating that a genetic predisposing factor is involved in this neurodegenerative disorder (Davies 1986; Fitch et al. 1988). In some families the disease segregates according to a clear autosomal dominant inheritance pattern (Davies 1986; Bird et al. 1988). Although there are large variations in age at onset of disease symptoms, duration of the illness, and clinical manifestation of the disease among these families, genetic linkage analysis of the pedigrees with polymorphic DNA markers may be helpful to localize the primary defect responsible for the disease in the families (Davies 1986; Botstein et al. 1980).
KeywordsGenetic Linkage Analysis Amyloid Precursor Protein Gene TaqI Polymorphism XbaI Polymorphism Previous Family History
Unable to display preview. Download preview PDF.
- Brun A (1983) In: Reisberg B (ed) Alzheimer’s disease; the standard reference, pp 37–47Google Scholar
- Raeymaekers P, Van Broeckhoven C, Backhovens H, Wehnert A, Muylle L, De Jonghe P, Gheuens J, Vandenberghe A (1988) The Duffy blood group is linked to the alpha spectrin locus in a large pedigree with autosomal dominant inheritance of Charcot-Marie-Tooth disease type 1. Hum Genet 78: 76–78PubMedCrossRefGoogle Scholar
- Roses AD, Pericak-Vance MA, Haynes CS, Haines JL, Gaskell PA, Yamaoka L, Yung WY, Heyman AL, Clark CM (1987) Linkage analysis in late onset familial Alzheimer’s disease ( AD ). Cytogenet Cell Genet 46: 684Google Scholar
- St. George-Hyslop PH, Tanzi RE, Polinsky RJ, Haines JL, Nee L, Watkins PC, Myers RH, Pollen D, Drachman D, Growden J, Bruni A, Foncin J-F, Salmon D, Frommelt P, Amaducci L, Sorbi S, Piacentini S, Stewart GD, Hobbs WJ, Conneally PM, Gusella JF (1987) The genetic defect causing familial Alzheimer’s disease maps on chromosome 21. Science 235: 885–890CrossRefGoogle Scholar
- Tanzi RE, Gusella JF, Watkins PC, Bruns GAp, St. George-Hyslop P, Van Keuren ML, Patterson D, Pagan S, Kurnit DM, Nevel RL (1987) Amyloid ß p[roteins gene: cDNA, mRNA distribution, and genetic linkage near the Alzheimer locus. Sciences 235:880–884Google Scholar
- Van Broeckhoven C, Genthe AM, Vandenberghe A, Horsthemke B, Backhovens H, Raeymaekers P, Van Hul W, Wehnert A, Gheuenes J, Cras P, Bruyland M, Martin JJ, Salbaum M, Multhaup G, Masters CL, Beyreuther K, Gurling HMD, Mullan MJ, Holland A, Barton A, Irving N, Williamson R, Richards SJ, Hardy JA (1987) Failure of familial Alzheimer’s disease to segregate with the A4-amyloid gene in several European families. Nature 329: 153–155PubMedCrossRefGoogle Scholar