Alzheimers (AD), Huntingtons (HD), and Parkinsons (PD) disease are age-related neurodegenerative disorders characterized by progressive neuronal cell death. three elderly patients with age-related pathology, of which two may have had possible prion disease. Results of a follow-up study in which marmoset monkeys were injected with AD brain homogenates, synthetic A-peptides, or CSF found approximately 3.5 years later that -amyloid seemed to be partially responsible for initiating or accelerating the process of cerebral amyloidosis (Ridley et al. 2006). In that regard, marmoset monkeys that were co-injected with -amyloid fibrils and lipopolysaccharide to elicit inflammation presented plaques 5 months post surgery, suggesting that the inflammation accelerated -amyloid deposition (Philippens et al. 2017). Contributions of NHP Research to Crenolanib pontent inhibitor the Improvement of AD Treatments Candidate AD therapeutic approaches can be grouped into neurorestorative and neuroprotective. Neurorestorative approaches using fetal tissue or stem cells to replace cholinergic neurons lost to the disease have been proposed (Sugaya 2003). Yet, the focus of the AD field has shifted towards the development of neuroprotective strategies due to the progressively widespread neurodegeneration and the complexity of the behaviors affected by AD. Lifestyle modification has been proposed to decrease AD risk. Healthy diet and exercise are typical medical suggestions, in part because obesity is associated with type II diabetes, which in turn increases the risk of AD (Grizzanti et al. 2016). NHP studies in calorie restriction (CR) support this concept. Rhesus macaques following a CR diet have significantly better glucose regulation than age-matched controls, greater preservation Crenolanib pontent inhibitor of gray matter in frontal and parietal cortices, and better learning of a motor task (Kastman et al. 2012). Postmortem brain analysis of CR monkeys compared to age-matched controls showed that CR modulates inflammation and offset the burden of oxidatively damaged proteins (Sridharan et al. 2014; Willette et al. 2013). The consequences of a sedentary life are not limited to weight gain but also decreased cognitive ability. Studies in middle-age rhesus macaques trained to run daily in a treadmill for a period of 5 months have shown that improved fitness increases both the rate of learning and blood Crenolanib pontent inhibitor flow to the cerebral cortex, at least during the period of regular exercise (Rhyu et al. 2010). In the last decade, a number of NHP preclinical and clinical trials evaluating neuroprotective strategies have been performed with differing levels of positive behavioral effects (Akwa et al. 2005). Although several trophic factors are available today, nerve growth factor (NGF) remains the favorite for AD treatment. Several lines of research have confirmed NGF support of cholinergic neurons and more recently have linked it to decreased amyloid burden (Triaca Crenolanib pontent inhibitor et al. 2016). NGF cannot cross the blood brain barrier; thus, it requires chronic intracerebral targeted delivery, as intracerebroventricular administration induces adverse side effects (Winkler et al. 1997). Studies in rodents and NHP models of AD have shown that NGF delivery by direct protein or therapy can protect cholinergic neurons from degeneration and sustain cholinergic function (Tuszynski et al. 1990). The safety, toxicity, and efficacy Crenolanib pontent inhibitor of autologous fibroblasts genetically modified to deliver NGF (Tuszynski et al. 1996) have been tested in NHPs before clinical trials. A phase I study has shown safety and some improvements (Tuszynski Rabbit Polyclonal to SLC30A4 et al. 2005). Postmortem analysis of patients that received the therapy a decade earlier.