Nature Genetics
2, 330 - 334 (1992)
doi:10.1038/ng1292-330
Genetic evidence for a novel familial Alzheimer's disease locus on chromosome 14P. St George-Hyslop1, J. Haines2, E. Rogaev1, 3, M. Mortilla1, 4, G. Vaula1, 5, M. Pericak-Vance6, J-F Foncin7, M. Montesi8, A. Bruni8, S. Sorbi4, I. Rainero5, L. Pinessi5, D. Pollen9, R. Polinsky10, L. Nee11, J. Kennedy12, F. Macciardi13, E. Rogaeva1, Y. Liang1, N. Alexandrova1, W. Lukiw1, K. Schlumpf2, R. Tanzi2, T. Tsuda14, L. Farrer15, J-M Cantu16, R. Duara17, L. Amaducci4, L. Bergamini5, J. Gusella2, A. Roses6
& D. Crapper McLachlan1
1Division of Neurology, Depts of Medicine and Physiology, Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, Ontario, Canada, M5S 1A8
2Molecular Neurogenetics Laboratory, Massachusetts General Hospital, CNY-6, Charlestown, Massachusetts 02129, USA
3National Research Center of Mental Health, Laboratory of Molecular Brain Genetics, Academy of Medical Sciences, Moscow, Russia, Zagorodnoe sh. 2/2, 113152
4Dept of Neurology, University of Florence, viale Morgagni 85, Firenze, Italy
5Dept of Neurology, University of Turin, via Cherasco 15, 10126-Torino, Italy
6Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, North Carolina, 27710, USA
7Laboratoire de Neurohistologie, Ecole Pratique des Hautes Etudes, La Salpéetrière, 75651 Paris CEDEK 13, France
8Servizio di Neurologia, USSL-17, CNR, via Trento, 88046, Lamezia Terme, Italy
9Dept of Neurology, University of Massachusetts Medical Center, 55 Lake Street, Worcester, Massachusetts, 01655, USA
10Sandoz Research Institute, Sandoz Pharmaceuticals Corporation, 59 Route 10, East Hanover, New Jersey, 07936, USA
11Clinical Neuropharmacology Section, NINDS, 9000 Rockville Pike, Bethesda, Maryland 20892, USA
12Neurogenetics Section, Clarke Institute of Psychiatry, Dept. of Psychiatry, University of Toronto, Toronto, Ontario, Canada M5T 1R8
13Dept. of Neurosciences, University of Milano School of Medicine, 20127- Milano, Italy
14Dept of Neurology, Tohoku University School of Medicine, Sendai, Japan
15Neurogenetics Laboratory, Boston University School of Medicine, Concord Ave, Boston, Massachusetts, USA
16Dept of Genetics, Istitituo Mexicano del Seguro Social, Guadalajara, Jalisco, Mexico
17Wein Center, Mt Sinai Medical Center, Miami Beach, Florida 33140, USA Familial Alzheimer's disease (FAD) has been shown to be genetically heterogeneous, with a very small proportion of early onset pedigrees being associated with mutations in the amyloid precursor protein (APP) gene on chromosome 21, and some late onset pedigrees showing associations with markers on chromosome 19. We now provide evidence for a major early onset FAD locus on the long arm of chromosome 14 near the markers D14S43 and D14S53 (multipoint lod score  = 23.4) and suggest that the inheritance of FAD may be more complex than had initially been suspected.
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