Transgenic Mice as a Model for Alzheimers Disease

Abstract

During the last few decades, numerous stable transgenic mouse strains have been developed in order to mimic a range of Alzheimer's disease (AD)-related pathologies. Although none of the models fully replicates the human disease, the models have been a key feature in translational research, providing significant insights into the pathophysiology of AD. They have also been widely used in the preclinical testing of potential therapies. The choice of transgenic mouse model, as well as the stage of Aβ pathology, significantly contributes to the outcome of the studies. Therefore, it is important to combine studies in different transgenic mouse models and detailed in vitro experiments to obtain a complete understanding of the origin of the disease, the actual sequences of early pathological events as well as being able to evaluate the effects of new drugs in the treatment of AD.

Antipsychotic, antidepressant, and cognitive-impairment properties of antipsychotics: rat profile and implications for behavioral and psychological symptoms of dementia

“…Such a screening battery could, theoretically, identify promising compounds for subsequent characterization in more advanced tests of anxio-depressive states and cognition. For example, drugs could then be tested for their capacity to reverse memory deficits elicited by muscarinic receptor antagonists such as scopolamine (Gravius et al 2011) and/or examine their effects in aged animals that suffer from impairment arising from decline in cerebral function or in mice that have been genetically modified to alter beta-amyloid expression and neurologically mimic Alzheimer’s disease (Lithner et al 2011). …”

Early-Onset Network Hyperexcitability in Presymptomatic Alzheimer’s Disease Transgenic Mice Is Suppressed by Passive Immunization with Anti-Human APP/Aβ Antibody and by mGluR5 Blockade

“…AD mouse models exhibit an age-dependent neuropathological process and cognitive decline. Most of the AD mouse models which harbor human APP mutation(s) and exhibit early-onset epileptiform activity and seizure susceptibility have increased intraneuronal human APP and Aβ prior to extracellular Aβ deposition and amyloid plaque formation (Oddo et al, 2003a,b; Billings et al, 2005; Lithner et al, 2011; Stargardt et al, 2015). In human AD brains, intraneuronal Aβ accumulation also precedes plaque formation (Gyure et al, 2001; Bossers et al, 2010).…”

Staging of cognitive deficits and neuropathological and ultrastructural changes in streptozotocin-induced rat model of Alzheimer’s disease

“…Modelling of brain insulin resistance is therefore relevant in this respect but has not been sufficiently studied. The identification of disease-causing mutations in proteins such as Aβ precursor protein (APP) and presenilins 1 and 2 (PS1, PS2) as well as pathogenic mutations in tau protein, resulted in development of many transgenic mice AD models (Lithner et al 2011). However, such models are representative for rare familial AD forms and their reliability as models for sAD has been recently questioned as well as their actual use in AD drug discovery (Bales 2012;Zach and Ashe 2010).…”