Genetic mouse models of brain ageing and Alzheimer's disease

Characterization of AD-like phenotype in aged APPSwe/PS1dE9 mice

“…Conversely, various 6-12-month-old AD mouse models, including PDAPP, TG2576, APP23, APP/ PS1, 5 × FAD, and 3 × Tg-AD do not show obvious hippocampal atrophy and neuronal loss (Bales 2012;Braidy et al 2012;Bilkei-Gorzo 2014;Webster et al 2014). Based on stereological analysis, we found that dorsal hippocampal volume and NeuN-positive neurons in 24-month-old APP/PS1 mice are reduced by 24.5 and 19.4 %, respectively (Fig.…”

“…There are several studies characterizing cognitive as well as noncognitive abnormality in APP/PS1 mice at 15-24 months of age (Morgan et al 2000;Arendash et al 2001;Sadowski et al 2004;Wilcock et al 2004;Hooijmans et al 2007;Minkeviciene et al 2008;Pistell et al 2008;Mei et al 2010;Ke et al 2011;Gengler et al 2012;Manczak and Reddy 2012;Wang et al 2012;Duffy and Hölscher 2013;Do et al 2014;Huang et al 2015;Janus et al 2015;Sahlholm et al 2015;Yousefi et al 2015) (A detailed summary is available in Table 2). However, the majority of experiments utilize young or adult APP/PS1 mice, which does not replicate typical hallmarks of AD, such as severe hippocampal atrophy and extensive neuronal loss (Bales 2012;Bilkei-Gorzo 2014). This shortcoming is then seen when positive therapeutic outcomes from APP/PS1 mice fail in clinical treatment on patients with AD (Bales 2012;Bilkei-Gorzo 2014).…”

“…However, the majority of experiments utilize young or adult APP/PS1 mice, which does not replicate typical hallmarks of AD, such as severe hippocampal atrophy and extensive neuronal loss (Bales 2012;Bilkei-Gorzo 2014). This shortcoming is then seen when positive therapeutic outcomes from APP/PS1 mice fail in clinical treatment on patients with AD (Bales 2012;Bilkei-Gorzo 2014). In order to provide a broader view of AD-like phenotype of this animal model, in this study, we systematically assessed behavioral and pathological changes of 24-month-old APP/PS1 mice.…”

“…Nevertheless, both types of AD show similar Aβ-related neuropathological changes (Huang and Mucke 2012). Correspondingly, various transgenic rodent models, such as those overexpressing mutant human APP or with both PS1 and tau, have been developed, providing valuable insights into specific aspects of AD pathogenesis (Bales 2012;Braidy et al 2012;Bilkei-Gorzo 2014;Webster et al 2014). Among these, APP/PS1 double transgenic mice are an extensively used model, showing progressive age-related development of Aβ accumulation and cognitive deficits (Jankowsky et al 2001;Trinchese et al 2004;van Groen et al 2006;Meyer-Luehmann et al 2009;Filali et al 2011;Janus et al 2015).…”

“…Contrary to humans, the overall survival rate of transgenic AD mice is similar to that of the wild-type (WT) littermate controls, but the underlying mechanism for this discrepancy remains unclear (Zahs and Ashe 2010;Webster et al 2014). Furthermore, to save experimental time and costs, most studies select young or adult transgenic mice, leaving out elderly subjects, as research participants (Bales 2012;Braidy et al 2012;Bilkei-Gorzo 2014). This is inconsistent with the fact that AD is essentially an agerelated disease.…”