Characterizing plasma biomarkers of Alzheimer’s disease in three non‐human primate species: marmosets, titi monkeys, and capuchins.

Background: Studies of aging in non‐human primates are important to elucidate primate‐specific mechanisms underlying human aging, including pathological trajectories like Alzheimer’s disease (AD). Evidence of AD‐like brain aging has been reported across the primate order including amyloid beta (AB) deposits, but blood‐based biomarkers are less well‐studied. The goal of this project was to explore the use of validated assays for plasma biomarkers in two new non‐human primate species: coppery titi monkeys (Plecturocebus cupreus) and brown capuchins (Sapajus apella).

Blood biomarkers and cognitive status in aged common marmosets.

Background: Nonhuman primates are arguably the best models for Alzheimer’s disease (AD), due to close similarities with humans in physiology and behavior, brain structure and function, and aging patterns. The common marmoset (Callithrix jacchus) is particularly valuable because it has the shortest lifespan of all anthropoids (10‐12 years), exhibits sex differences in age‐related cognitive decline and develops AD‐like pathology with age. In the present study, we investigated blood‐based biomarkers in male and female marmosets with cognitive and neuropathological assessments.

Oral administration of ethinyl estradiol and the brain-selective estrogen prodrug DHED in a female common marmoset model of menopause: Effects on cognition, thermoregulation, and sleep.

Menopausal symptoms of sleep disturbances, cognitive deficits, and hot flashes are understudied, in part due to the lack of animal models in which they co-occur. Common marmosets (Callithrix jacchus) are valuable nonhuman primates for studying these symptoms, and we examined changes in cognition (reversal learning), sleep (48 h/wk of sleep recorded by telemetry), and thermoregulation (nose temperature in response to mild external warming) in middle-aged, surgically-induced menopausal marmosets studied at baseline, during 3-week phases of ethinyl estradiol (EE, 4 μg/kg/day, p.o.

Expression of bond-related behaviors affects titi monkey responsiveness to oxytocin and vasopressin treatments.

Social bonds influence physiology and behavior, which can shape how individuals respond to physical and affective challenges. Coppery titi monkey (Plecturocebus cupreus) offspring form selective bonds with their fathers, making them ideal for investigating how father-daughter bonds influence juveniles' responses to oxytocin (OT) and arginine-vasopressin (AVP) manipulations. We quantified the expression of father-daughter bond-related behaviors in females (n = 10) and gave acute intranasal treatments of saline, low/medium/high OT, low/high AVP, or an OT receptor antagonist (OTA) to subjects prior to a parent preference test.

Titi monkey father-daughter bond-related behaviors explain stress response variability.

Social interactions regulate our behavior and physiology, and strong social bonds can buffer us from stress. Coppery titi monkeys (Plecturocebus cupreus) are socially monogamous South American monkeys that display strong social bonds. Infants form selective bonds with their fathers, making them ideal for studying father-daughter bonds.

Neuronal vulnerability to brain aging and neurodegeneration in cognitively impaired marmoset monkeys (Callithrix jacchus).

The investigation of neurobiological and neuropathological changes that affect synaptic integrity and function with aging is key to understanding why the aging brain is vulnerable to Alzheimer's disease. We investigated the cellular characteristics in the cerebral cortex of behaviorally characterized marmosets, based on their trajectories of cognitive learning as they transitioned to old age. We found increased astrogliosis, increased phagocytic activity of microglial cells and differences in resting and reactive microglial cell phenotypes in cognitively impaired compared to nonimpaired marmosets.

Long term effects of chronic intranasal oxytocin on adult pair bonding behavior and brain glucose uptake in titi monkeys (Plecturocebus cupreus).

Intranasal oxytocin (IN OXT) administration has been proposed as a pharmacological treatment for a range of biomedical conditions including neurodevelopmental disorders. However, studies evaluating the potential long-lasting effects of chronic IN OXT during development are still scarce. Here we conducted a follow-up study of a cohort of adult titi monkeys that received intranasal oxytocin 0.

Positivity resonance in long-term married couples: Multimodal characteristics and consequences for health and longevity.

The Positivity Resonance Theory of coexperienced positive affect describes moments of interpersonal connection characterized by shared positive affect, caring nonverbal synchrony, and biological synchrony. The construct validity of positivity resonance and its longitudinal associations with health have not been tested. The current longitudinal study examined whether positivity resonance in conflict interactions between 154 married couples predicts health trajectories over 13 years and longevity over 30 years.

Sex differences in cognitive aging: a 4-year longitudinal study in marmosets.

Longitudinal studies are essential to understand healthy and pathological neurocognitive aging such as Alzheimer's Disease, but longitudinal designs are rare in both humans and non-human primate models of aging because of the difficulty of tracking cognitive change in long-lived primates. Common marmosets (Callithrix jacchus) are uniquely suited for aging studies due to their naturally short lifespan (10-12 years), sophisticated cognitive and social abilities and Alzheimer Disease-like neuropathology. We report the first longitudinal study of cognitive aging in marmosets (N = 28) as they transitioned from middle- (∼5 years) to old age (∼9 years).

Nonhuman primates at the intersection of aging biology, chronic disease, and health: An introduction to the American Journal of Primatology Special Issue on aging, cognitive decline, and neuropathology in nonhuman primates.

Aging across the Primate Order is poorly understood because ages of individuals are often unknown, there is a dearth of aged animals available for study, and because aging is best characterized by longitudinal studies which are difficult to carry out in long-lived species. The human population is aging rapidly, and advanced age is a primary risk factor for several chronic diseases and conditions that impact healthspan. As lifespan has increased, diseases and disorders of the central nervous system (CNS) have become more prevalent, and Alzheimer's disease and related dementias have become epidemic.

The marmoset as an important primate model for longitudinal studies of neurocognitive aging.

Age-related cognitive decline has been extensively studied in humans, but the majority of research designs are cross-sectional and compare across younger and older adults. Longitudinal studies are necessary to capture variability in cognitive aging trajectories but are difficult to carry out in humans and long-lived nonhuman primates. Marmosets are an ideal primate model for neurocognitive aging as their naturally short lifespan facilitates longitudinal designs.

Physiological linkage during shared positive and shared negative emotion.

Physiological linkage refers to the degree to which peoples' physiological responses change in coordinated ways. Here, we examine whether and how physiological linkage relates to incidents of shared emotion, distinguished by valence. Past research has used an "overall average" approach and characterized how physiological linkage over relatively long time periods (e.

Relationship tenure differentially influences pair-bond behavior in male and female socially monogamous titi monkeys (Callicebus cupreus).

Pair-bonded primates have uniquely enduring relationships and partners engage in a suite of behaviors to maintain these close bonds. In titi monkeys, pair bond formation has been extensively studied, but changes across relationship tenure remain unstudied. We evaluated differences in behavioral indicators of pair bonding in newly formed (~6 months paired, n = 9) compared to well-established pairs (average 3 years paired, n = 8) of titi monkeys (Callicebus cupreus) as well as sex differences within the pairs.

Effects of chronic intranasal oxytocin on behavior and cerebral glucose uptake in juvenile titi monkeys.

Intranasal oxytocin (IN OXT) has been proposed as a treatment for autism spectrum disorder (ASD); however, little is known about the effects of long-term exposure. This is the first study in a non-human primate species to examine how developmental exposure to chronic IN OXT affects juvenile's interactions with family members, social preference for parents versus strangers, anxiety-like behavior, and cerebral glucose metabolism. Titi monkeys are socially monogamous and biparental; their family bonds share important characteristics with human family bonds.

Dopamine D1-like receptors regulate agonistic components of pair bond maintenance behaviors in male titi monkeys (Callicebus cupreus).

Several neurobiological mechanisms are implicated in the formation of selective pair bonds in socially monogamous mammals, however much less is known about the mechanisms that underlie the long-term behavioral maintenance of these bonds. In prairie voles (Microtus ochrogaster), agonistic behavior that contributes to pair bond maintenance are regulated by dopamine activity at D1-like receptors (D1R) within the mesocorticolimbic system. Evidence suggests D1Rs similarly regulate the behavioral components of pair bond maintenance in socially monogamous titi monkeys (Callicebus cupreus); however, evaluation with behavioral pharmacology is necessary to evaluate this hypothesis.

Development of a partner preference test that differentiates between established pair bonds and other relationships in socially monogamous titi monkeys (Callicebus cupreus).

Partner preference, or the selective social preference for a pair mate, is a key behavioral indicator of social monogamy. Standardized partner preference testing has been used extensively in rodents but a single test has not been standardized for primates. The goal of this study was to develop a partner preference test with socially monogamous titi monkeys (Callicebus cupreus) adapted from the widely used rodent test.

Cooperatively breeding cottontop tamarins (Saguinus oedipus) do not donate rewards to their long-term mates.

This study tested the hypothesis that cooperative breeding facilitates the emergence of prosocial behavior by presenting cottontop tamarins (Saguinus oedipus) with the option to provide food rewards to pair-bonded mates. In Experiment 1, tamarins could provide rewards to mates at no additional cost while obtaining rewards for themselves. Contrary to the hypothesis, tamarins did not demonstrate a preference to donate rewards, behaving similar to chimpanzees in previous studies.