Alzheimer’s Disease (AD), the most prevalent neurodegenerative disease of aging, affects one in eight older Americans. Nearly all drug treatments tested for AD today have failed to show any efficacy. There is a great need for therapies to prevent and/or slow the progression of AD. The major challenge in AD drug development is lack of clarity about the mechanisms underlying AD pathogenesis and pathophysiology. Several studies support the notion that AD is a multifactorial disease. While there is abundant evidence that amyloid plays a role in AD pathogenesis, other mechanisms have been implicated in AD such as tangle formation and spread, dysregulated protein degradation pathways, neuroinflammation, and loss of support by neurotrophic factors. Therefore, current paradigms of AD drug design have been shifted from single target approach (primarily amyloid-centric) to developing drugs targeted at multiple disease aspects, and from treating AD at later stages of disease progression to focusing on preventive strategies at early stages of disease development. Here, we summarize current strategies and new trends of AD drug development, including pre-clinical and clinical trials that target different aspects of disease (mechanism-based versus non-mechanism based, e.g. symptomatic treatments, lifestyle modifications and risk factor management).

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The tree shrews are non-rodent, primate-like, small animals. There is increasing interest in using them to establish animal models for medical and biological research. This review focuses on the use of the tree shrews in in vivo studies on viral hepatitis, hepatocellular carcinoma (HCC), myopia, and psychosocial stress. Because of the susceptibility of the tree shrews (Tupaia belangeri) and their hepatocytes to infection with human hepatitis B virus (HBV) in vivo and in vitro, these animals have been used to establish human hepatitis virus-induced hepatitis and human HBV- and aflatoxin B1-associated HCC models. As these animals are phylogenetically close to primates in evolution and have a well-developed visual system and color vision in some species, they have been utilized to establish myopia models. Because dramatic behavioral, physiological, and neuroendocrine changes in subordinate male tree shrews are similar to those observed in depressed human patients, the tree shrews have been successfully employed to experimentally study psychosocial stress. However, the tree shrews holds significant promise as research models and great use could be made of these animals in biomedical research.