Mutant genes in familial Alzheimer's disease and transgenic models

Annual Review of Neuroscience
D L Price, S S Sisodia

Abstract

The most common cause of dementia occurring in mid- to late-life is Alzheimer's disease (AD). Some cases of AD, particularly those of early onset, are familial and inherited as autosomal dominant disorders linked to the presence of mutant genes that encode the amyloid precursor protein (APP) or the presenilins (PS1 or PS2). These mutant gene products cause dysfunction/death of vulnerable populations of nerve cells important in memory, higher cognitive processes, and behavior. AD affects 7-10% of individuals > 65 years of age and perhaps 40% of individuals > 80 years of age. For the late-onset cases, the principal risk factors are age and apolipoprotein (apoE) allele type, with apoE4 allele being a susceptibility factor. In this review, we briefly discuss the clinical syndrome of AD and the neurobiology/neuropathology of the disease and then focus attention on mutant genes linked to autosomal dominant familial AD (FAD), the biology of the proteins encoded by these genes, and the recent exciting progress in investigations of genetically engineered animal models that express these mutant genes and develop some features of AD.

References

Nov 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·W WascoF Solomon
Nov 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·J D BuxbaumP Greengard
Nov 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·A KammesheidtR L Neve
Sep 1, 1992·Neurobiology of Aging·D L PriceS S Sisodia
Apr 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·R L NeveC F Hohmann
Jul 1, 1992·Journal of Neuropathology and Experimental Neurology·E MasliahR D Terry
Jul 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·S S Sisodia
Feb 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·E H KooD L Price
May 15, 1986·Neuroscience Letters·R G StrubleM R DeLong
Nov 30, 1989·Biochemical and Biophysical Research Communications·M R PalmertS G Younkin
Aug 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·M R PalmertS G Younkin
Nov 10, 1989·JAMA : the Journal of the American Medical Association·D A EvansJ O Taylor
Feb 20, 1987·Science·P H St George-HyslopD Drachman
Jun 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·C L MastersK Beyreuther
May 16, 1984·Biochemical and Biophysical Research Communications·G G Glenner, C W Wong

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Citations

Feb 24, 2001·Annals of Neurology·M J SmithW S Brooks
Jun 8, 2001·Biochemical and Biophysical Research Communications·R HataT Sawada
Mar 17, 2011·Brain Structure & Function·Marijke A M LemmensChristoph Schmitz
Jun 11, 2008·Neuromolecular Medicine·Esther S OhStina M Fangmark Tucker
Mar 23, 2011·Molecular Neurobiology·Daniel W WessonDonald A Wilson
May 21, 2008·Cell Stress & Chaperones·Sun Don Kim, Jinoh Kim
May 12, 2004·Biochimica Et Biophysica Acta·Wenyan WangCorey Strickland
Apr 27, 2005·Brain Research. Brain Research Reviews·Thomas van Groen, Inga Kadish
Mar 10, 2004·Neurobiology of Disease·I GurevicieneH Tanila
Jun 23, 2004·Neurobiology of Disease·Cathy MitchelmoreNiels A Jensen
Dec 31, 2003·Trends in Neurosciences·José A Esteban
Nov 26, 2003·Experimental Neurology·Véronique BlanchardLaurent Pradier
Sep 22, 2001·Physiology & Behavior·C Janus, D Westaway
Jul 7, 1999·Neuroscience and Biobehavioral Reviews·E Gahtan, J B Overmier
Aug 17, 2001·Trends in Neurosciences·P Aebischer, J Ridet
Mar 8, 2002·Trends in Neurosciences·S S SisodiaB De Strooper
May 4, 2001·Trends in Genetics : TIG·P F ChapmanM F Ramsay
Dec 25, 2002·Neurobiology of Aging·P H KellyB Sommer
Dec 15, 2000·Progress in Neurobiology·M F Mehler, S Gokhan
Nov 22, 2001·Maturitas·F MassartM L Brandi
May 26, 2001·Clinics in Geriatric Medicine·D Galasko
Dec 16, 1998·Research in Immunology·V H PerryS Betmouni
Feb 13, 2001·Current Opinion in Cell Biology·M L Garcia, D W Cleveland
Nov 13, 1998·Current Opinion in Neurobiology·M GoedertS W Davies
Sep 29, 2012·Journal of Medicinal Chemistry·Ylva GravenforsFredrik Rahm
Nov 7, 2012·Journal of Medicinal Chemistry·Tobias GinmanFredrik Rahm
Oct 15, 1998·Nature Medicine·R E Tanzi
Dec 19, 2009·Cell Death and Differentiation·L BaroncelliL Maffei

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Methods Mentioned

BETA
transgenic
two-hybrid
acylation
gel filtration
ELISA

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