Behavioral phenotypes of amyloid-based genetically modified mouse models of Alzheimer's disease.
Alzheimer's disease (AD) is the most common neurodegenerative affliction of the elderly, presenting with progressive memory loss and dementia and terminating with death. There have been significant advances in understanding the biology and subsequent diagnosis of AD; however, the furious pace of research has not yet translated into a disease-modifying treatment. While scientific inquiry in AD is largely centered on identifying biological players and pathological mechanisms, the day-to-day realities of AD patients and their caregivers revolve around their steady and heartbreaking cognitive decline. In the past decade, AD research has been fundamentally transformed by the development of genetically modified animal models of amyloid-driven neurodegeneration. These important in vivo models not only replicate some of the hallmark pathology of the disease, such as plaque-like amyloid accumulations and astrocytic inflammation, but also some of the cognitive impairments relevant to AD. In this article, we will provide a detailed review of the behavioral and cognitive deficits present in several transgenic mouse models of AD and discuss their functional changes in response to experimental treatments.
Kobayashi
D T
DT
Pharmacology Department, Elan Pharmaceuticals, South San Francisco, CA 94080, USA.
Chen
K S
KS
D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism; D053829:Amyloid Precursor Protein Secretases; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D016282:Aspartic Acid Endopeptidases; D001522:Behavior, Animal / Q000502:physiology*; D003072:Cognition Disorders / Q000235:genetics; D004195:Disease Models, Animal; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism; D005824:Genetics, Behavioral; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic / Q000235:genetics*; D010641:Phenotype; D053764:Presenilin-1; D053766:Presenilin-2
D016564:Amyloid beta-Protein Precursor; D008565:Membrane Proteins; D053764:Presenilin-1; D053766:Presenilin-2; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509282:Bace1 protein, mouse; D008666:Metalloendopeptidases