Nonhuman primates (NHPs) are important to study the pathophysiology of neurodegenerative disease and evaluate therapies targeting the central nervous system (CNS). Understanding the age‐associated incidence of natural CNS pathology in a given NHP species is critical to assess the safety of potential treatments for neurodegenerative disorders like Alzheimer's disease (AD). We describe background and age‐related neuropathology in the St. Kitts African green monkey (AGM), a recognized translational model for neurodegenerative research, additionally defining the age progression of AD‐associated neuropathology in this species. Seventy‐one AGM brains were examined, representing age groups of 3–6 years (n = 20), 7–9 years (n = 20), 10–15 years (n = 20), and >15 years (n = 11). A subset of brains (n = 31) was assessed immunohistochemically for AD‐related pathology, including expressions of Aβ, tau, and GFAP. Age‐related microscopic findings included hemosiderosis, spheroid formation, neuronal lipofuscinosis and neuromelanosis, white matter and neuropil vacuolation, astrocytosis, and focal microgliosis. Non‐age‐related findings included perivascular ceroid‐laden macrophages, meningeal melanosis, and vascular mineralization. Immunohistochemistry revealed 4G8‐immunopositive Aβ plaques and vascular deposits in the prefrontal, frontal, cingulate, and temporal cortices of nine animals over 15 years of age, with associated increase in GFAP expression. In 12 animals, 11 over the age of 10 years, phosphorylated tau CP13‐immunoreactive neurons, neuropil, and oligodendrocyte‐like cells were seen in the prefrontal, frontal, cingulate, orbital, temporal, and entorhinal cortices as well as the hippocampus; no neurofibrillary tangles were observed. AD‐related pathology showed an age‐related development in cognitive‐associated areas in the AGM, highlighting the value of the AGM as a natural model for these neurodegenerative diseases.

Age-related macular degeneration (AMD) is the leading cause of central retinal vision loss worldwide, with an estimated 1 in 10 people over the age of 55 showing early signs of the condition. There are currently no forms of therapy available for the end stage of dry AMD, geographic atrophy (GA). Here, we show that the inner blood-retina barrier (iBRB) is highly dynamic and may play a contributory role in GA development. We have discovered that the gene CLDN5, which encodes claudin-5, a tight junction protein abundantly expressed at the iBRB, is regulated by BMAL1 and the circadian clock. Persistent suppression of claudin-5 expression in mice exposed to a cholesterol-enriched diet induced striking retinal pigment epithelium (RPE) cell atrophy, and persistent targeted suppression of claudin-5 in the macular region of nonhuman primates induced RPE cell atrophy. Moreover, fundus fluorescein angiography in human and nonhuman primate subjects showed increased retinal vascular permeability in the evening compared with the morning. These findings implicate an inner retina-derived component in the early pathophysiological changes observed in AMD, and we suggest that restoring the integrity of the iBRB may represent a novel therapeutic target for the prevention and treatment of GA secondary to dry AMD.

Background Management of diabetes remains a major health and economic challenge, demanding test systems in which to develop new therapies. These studies assessed different methodologies for determining glucose tolerance in green monkeys. Methods Twenty-eight African green monkeys between 4 and 24 years old underwent single or repeat intravenous glucose tolerance testing (IVGTT), oral glucose tolerance testing (OGTT), and/or graded glucose infusion testing. Results Geriatric monkeys exhibited glucose intolerance with impaired glucose-stimulated insulin secretion following IVGTT. Repeat IVGTT and OGTT assessments were inconsistent. Monkeys with low glucose-stimulated insulin secretion after graded glucose infusion exhibited elevated blood glucose levels. Conclusion IVGTT and graded glucose infusion protocols revealed differences in glucose tolerance among green monkeys at single time points, including age-dependent differences suggestive of shifts in pancreatic beta-cell functional capacity, but care should be applied to study design and the interpretation of data in the setting of longitudinal studies.

The use of the St. Kitts green monkey (Chlorocebus Sabaeus) in safety pharmacology is not as well documented as other primates, but is gaining popularity as the importance of a more genetically homogeneous primate species for use in biomedical research is being understood. In this test system we have characterized Stellar TSE telemetry devices for acquiring left ventricular pressure (LVP), systemic blood pressure (BP), epicardial electrocardiography (ECG) and core body temperature. In the current study 4 normotensive monkeys were implanted. The systemic pressure catheter was advanced from the internal iliac to the mid aorta. The transmitter body was anchored to the abdominal wall, and the bio-potential leads and LVP catheter were tunneled to the left thorax. LVP was acquired and the bio-potential leads placed for epicardial ECG. Systemic BP, LVP, HR and ECG parameters were determined. Fifteen seconds of data were collected every 30 min for a 48 hr period. The mean for each test parameter were calculated for each 48h acquisition session and subsequently averaged over the in-life duration of the study. The mean systemic systolic, diastolic and pulse pressures as well as heart rate (from LVP) have been stable and consistent with expectation. The mean LV systolic, LV diastolic, mean LVP, pulse pressure as well as the heart rate (from ECG) have been slightly higher in 3 of the 4 monkeys at later time points compared to baseline, possibly due to the use of a shorter catheter that may be squeezed by the ventricular wall, for which reason a longer catheter model has been designed for subsequent studies. To date (6 months), the data generated with the TSE system have been comparable to other telemetry devices and has further supported the green monkey as an acceptable and reliable primate alternative for safety pharmacology or combination cardiovascular/toxicology studies.

BackgroundHematology and clinical chemistry (HCC) reference values are critical in veterinary practice and in vivo pre-clinical research, enabling detection of health abnormalities, response to therapeutic intervention or adverse toxicological effects, as well as monitoring of clinical management.MethodsIn this report, reference ranges for 46 HCC parameters were characterized in 331 wild-caught and colony-bred African green monkeys. Effects of sex, weight and duration of captivity were determined by one-way analysis of variance.ResultsSignificant sex differences were observed for several HCC parameters. Significant differences were also observed for select HCC variables between newly caught animals and those held in captivity for 1-12 months or longer.ConclusionsComparison of this data with other non-human primate species and humans highlights similarities and disparities between species. Potential causes of interpopulation variability and relevance to the use of the African green monkey as a non-human primate model are discussed.