Tau is central in the genetic Alzheimer–frontotemporal dementia spectrum

Department of Molecular Genetics (VIB 8), Flanders Interuniversity Institute for Biotechnology, Neurodegenerative Brain Diseases Group, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, B-2610 Antwerpen, Belgium.
Trends in Genetics (Impact Factor: 9.92). 01/2006; 21(12):664-72. DOI: 10.1016/j.tig.2005.09.005
Source: PubMed


In contrast to the common and genetically complex senile form of Alzheimer's disease (AD), the molecular genetic dissection of inherited presenile dementias has given important mechanistic insights into the pathogenesis of degenerative brain disease. Here, we focus on recent genotype-phenotype correlative studies in presenile AD and the frontotemporal dementia (FTD) complex of disorders. Together, these studies suggest that AD and FTD are linked in a genetic spectrum of presenile degenerative brain disorders in which tau appears to be the central player.

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Available from: Christine Van Broeckhoven
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    • "Here, we review the contribution of Drosophila to the molecular understanding of Tau neurotoxicity, a central player in the AD-FTD spectrum of disorders [9]. We give a brief overview of the most commonly used genetic tools in Drosophila and summarize the different available Tau models and readouts for Tau neurotoxicity. "
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    • "Thus, understanding the nature of attention deficits in early AD may provide insights into the mechanisms that dissociate AD from normal aging. Mutations in genes encoding β-amyloid precursor protein (APP) or presenilin 1 lead to inherited, early onset forms of AD (Haass 1997, Selkoe 1998), and mutations in the microtubule-associated protein tau cause some cases of frontotemporal lobe dementia (Dermaut et al., 2005). Transgenic mice overexpressing these altered human genes develop age-dependent learning and memory deficits, thus mimicking important behavioural aspects of the disease (Götz and Ittner 2008). "
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    • "A number of neurodegenerative disorders are caused by mutations in genes expressed principally in the central nervous system. This is the case for the brain proteins tau and α-synuclein, which are genetically linked to autosomal dominant forms of frontotemporal dementia [214] and PD [215], respectively. Recently, we postulated that susceptibility to AD could come from genes predominantly expressed in affected brain regions, such as the hippocampus. "
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