TY - JOUR
T1 - Alzheimer's disease
T2 - Genetic studies and transgenic models
AU - Price, Donald L.
AU - Tanzi, Rudolph E.
AU - Borchelt, David R.
AU - Sisodia, Sangram S.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 1998
Y1 - 1998
N2 - Recent advances in a variety of areas of research, particularly in genetics and in transgenic (Tg)/gene targeting approaches, have had a substantial impact on our understanding of Alzheimer's disease (AD) and related disorders. After briefly reviewing the progress that has been made in diagnostic assessments of patients with senile dementia and in investigations of the neuropathology of AD, we discuss some of the genes/proteins that are causative or risk factors for this disease, including those encoding amyloid precursor protein, presenilin 1 and 2, and apolipoprotein E. In addition, we comment on several potential new candidate loci/genes. Subsequently, we review selected recent reports of analyses of a variety of lines of Tg mice that show several neuropathological features of AD, including Aβ-amyloid deposits and dystrophic neurites. Finally, we discuss the several important issues in future investigations of Tg mice, with particular emphasis on the influences of genetic strains on phenotype, especially behavior, and strategies for making new models of neurodegenerative disorders. We believe that investigations of these Tg models will (a) enhance understanding of the relationships between impaired performance on memory tasks and the pathological/biochemical abnormalities in brain, (b) help to clarify pathogenic mechanisms in vivo, (c) lead to identification of new therapeutic targets, and (d) allow testing of new treatment strategies first in mice and then, if successful, in humans with AD.
AB - Recent advances in a variety of areas of research, particularly in genetics and in transgenic (Tg)/gene targeting approaches, have had a substantial impact on our understanding of Alzheimer's disease (AD) and related disorders. After briefly reviewing the progress that has been made in diagnostic assessments of patients with senile dementia and in investigations of the neuropathology of AD, we discuss some of the genes/proteins that are causative or risk factors for this disease, including those encoding amyloid precursor protein, presenilin 1 and 2, and apolipoprotein E. In addition, we comment on several potential new candidate loci/genes. Subsequently, we review selected recent reports of analyses of a variety of lines of Tg mice that show several neuropathological features of AD, including Aβ-amyloid deposits and dystrophic neurites. Finally, we discuss the several important issues in future investigations of Tg mice, with particular emphasis on the influences of genetic strains on phenotype, especially behavior, and strategies for making new models of neurodegenerative disorders. We believe that investigations of these Tg models will (a) enhance understanding of the relationships between impaired performance on memory tasks and the pathological/biochemical abnormalities in brain, (b) help to clarify pathogenic mechanisms in vivo, (c) lead to identification of new therapeutic targets, and (d) allow testing of new treatment strategies first in mice and then, if successful, in humans with AD.
KW - Dystrophic neurites
KW - Presenilin 1 and 2
KW - Senile dementia
KW - Tg mice
KW - β-Amyloid precursor protein
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U2 - 10.1146/annurev.genet.32.1.461
DO - 10.1146/annurev.genet.32.1.461
M3 - Review article
C2 - 9928488
AN - SCOPUS:0032413192
SN - 0066-4197
VL - 32
SP - 461
EP - 493
JO - Annual review of genetics
JF - Annual review of genetics
ER -