DEMENTIAS - REVIEW ARTICLE Recent rodent models for Alzheimer’s disease: clinical implications and basic research Nady Braidy • Pablo Mun ˜oz • Adrian G. Palacios • Gloria Castellano-Gonzalez • Nibaldo C. Inestrosa • Roger S. Chung • Perminder Sachdev • Gilles J. Guillemin Received: 26 May 2011 / Accepted: 24 October 2011 / Published online: 16 November 2011 Ó Springer-Verlag 2011 Abstract Alzheimer’s disease (AD) is the most common origin of dementia in the elderly. Although the cause of AD remains unknown, several factors have been identified that appear to play a critical role in the development of this debilitating disorder. In particular, amyloid precursor pro- tein (APP), tau hyperphosphorylation, and the secretase enzymes, have become the focal point of recent research. Over the last two decades, several transgenic and non- transgenic animal models have been developed to elucidate the mechanistic aspects of AD and to validate potential therapeutic targets. Transgenic rodent models over- expressing human b-amyloid precursor protein (b-APP) and mutant forms of tau have become precious tools to study and understand the pathogenesis of AD at the molecular, cellular and behavioural levels, and to test new therapeutic agents. Nevertheless, none of the transgenic models of AD recapitulate fully all of the pathological features of the disease. Octodon degu, a South American rodent has been recently found to spontaneously develop neuropathological signs of AD in old age. This review aims to address the limitations and clinical relevance of trans- genic rodent models in AD, and to highlight the potential for O. degu as a natural model for the study of AD neuropathology. Keywords Alzheimer’s disease Á Animal models Á Octodon degu Á Amyloid-b Á Tau phosphorylation Á Transgenic models Introduction Alzheimer’s disease (AD) is the most common cause of dementia, characterised by progressive memory loss and neurodegeneration in the cerebral cortex (Maccioni et al. 2001). The two pathological hallmarks of AD are neuro- filament tangles (NFT) and neuritic plaques. NFT are intracellular twisted nerve cell fibers composed of hyper- phosphorylated tau, a low molecular weight microtubule- associated protein (Glenner and Wong 1984). The core component of plaques is b amyloid (Ab) (Glenner and Wong 1984). Ab peptides are typically *4 kDa b-pleated sheet peptides with different N- and C-terminal endings that are N. Braidy Á G. J. Guillemin (&) Department of Pharmacology, University of New South Wales, Sydney, NSW 2052, Australia e-mail: g.guillemin@unsw.edu.au N. Braidy Á P. Sachdev School of Psychiatry, University of New South Wales, Sydney, Australia P. Mun ˜oz Á A. G. Palacios Centro Interdiciplinario de Neurociencia de Valparaiso (CINV), Facultad de Ciencias, Universidad de Valparaiso, Valparaiso, Chile G. Castellano-Gonzalez Á G. J. Guillemin St Vincent’s Centre for Applied Medical Research, Sydney, Australia N. C. Inestrosa Centre for Aging and Regeneration (CARE), Faculty of Biological Sciences, P. Catholic University of Chile, Santiago, Chile R. S. Chung Menzies Research Institute, University of Tasmania, Hobart, Australia P. Sachdev Neuropsychiatric Institute, Prince of Wales Hospital, Sydney, Australia 123 J Neural Transm (2012) 119:173–195 DOI 10.1007/s00702-011-0731-5