Animal models of Alzheimer's disease and frontotemporal dementia.
Insoluble protein aggregates have been linked to Alzheimer's disease (AD) and frontotemporal dementia (FTD). Recent work in transgenic mice has shed light on the role of these aggregates by identifying soluble oligomeric species that may interfere with essential cellular mechanisms at an early disease stage. This review summarizes what we have learned about the roles of these proteins from transgenic mice and invertebrate species such as flies and worms. Proteomic and transcriptomic analyses of tissue from these animal models have identified new molecules with crucial roles in disease. Moreover, transgenic animals have been instrumental in defining drug targets and designing novel therapeutic strategies. With advanced imaging techniques that can be used in both humans and mice an early, preclinical diagnosis of AD and FTD could be within reach.
Götz
Jürgen
J
Alzheimer's & Parkinson's Disease Laboratory, Brain & Mind Research Institute, University of Sydney, 100 Mallett Street, Camperdown, NSW 2050, Australia. jgoetz@med.usyd.edu.au
Ittner
Lars M
LM
D000544:Alzheimer Disease / Q000175:diagnosis / Q000473:pathology / Q000503:physiopathology*; D000595:Amino Acid Sequence; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D053327:Apolipoprotein E4 / Q000235:genetics / Q000378:metabolism; D001522:Behavior, Animal / Q000502:physiology; D003704:Dementia / Q000175:diagnosis / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D006801:Humans; D008969:Molecular Sequence Data; D009483:Neuropsychological Tests; D016415:Sequence Alignment; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism
D016564:Amyloid beta-Protein Precursor; D053327:Apolipoprotein E4; D016875:tau Proteins; D053829:Amyloid Precursor Protein Secretases