Alzheimer's disease: Genetic studies and transgenic models

Donald L. Price, Rudolph E. Tanzi, David R. Borchelt, Sangram S. Sisodia

Research output: Contribution to journalReview articlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)461-493
Number of pages33
JournalAnnual review of genetics
Volume32
DOIs
StatePublished - 1998

Keywords

  • Dystrophic neurites
  • Presenilin 1 and 2
  • Senile dementia
  • Tg mice
  • β-Amyloid precursor protein

ASJC Scopus subject areas

  • Genetics

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