Basic Science and Pathogenesis.

Background: Mediterranean diets may reduce Alzheimer's disease (AD) risk and preserve cognitive function relative to Western diets by protecting against inflammation. In a long term controlled randomized trial of Mediterranean vs. Western diet consumption in cynomolgus macaques (Macaca fascicularis), difficult to conduct in humans, we found significant anti-inflammatory effects of Mediterranean diet on circulating monocyte and brain temporal cortex transcriptional profiles.

Basic Science and Pathogenesis.

Background: Western and Mediterranean diets differentially affect cerebral cortical gene expression, brain structure, and socioemotional behavior in middle-aged female nonhuman primates (NHP) (Macaca fascicularis). In this study, we investigate the effect of diet on brain molecular composition.

Method: Using a machine learning approach, we quantified the impact of these diets on the presynaptic proteome in the lateral temporal cortex determined by synaptometry by time of flight (SynTOF) mass spectrometry and examined associations between the proteome, transcriptome, and an array of multisystem phenotypes.

DJ-1-mediated repression of the RNA-binding protein FMRP is predicted to impact known Alzheimer's disease-related protein networks.

Background: RNA-binding proteins (RBPs) modulate the synaptic proteome and are instrumental in maintaining synaptic homeostasis. Moreover, aberrant expression of an RBP in a disease state would have deleterious downstream effects on synaptic function. While many underlying mechanisms of synaptic dysfunction in Alzheimer's disease (AD) have been proposed, the contribution of RBPs has been relatively unexplored.

Mediterranean diet protects against a neuroinflammatory cortical transcriptome: Associations with brain volumetrics, peripheral inflammation, social isolation, and anxiety in nonhuman primates (Macaca fascicularis).

Mediterranean diets may be neuroprotective and prevent cognitive decline relative to Western diets; however, the underlying biology is poorly understood. We assessed the effects of Western versus Mediterranean-like diets on RNAseq-generated transcriptional profiles in lateral temporal cortex and their relationships with longitudinal changes in neuroanatomy, circulating monocyte gene expression, and observations of social isolation and anxiety in 38 socially-housed, middle-aged female cynomolgus macaques (Macaca fascicularis). Diet resulted in differential expression of seven transcripts (FDR < 0.

Aberrant DJ-1 expression underlies L-type calcium channel hypoactivity in dendrites in tuberous sclerosis complex and Alzheimer's disease.

L-type voltage-gated calcium (Ca) channels (L-VGCC) dysfunction is implicated in several neurological and psychiatric diseases. While a popular therapeutic target, it is unknown whether molecular mechanisms leading to disrupted L-VGCC across neurodegenerative disorders are conserved. Importantly, L-VGCC integrate synaptic signals to facilitate a plethora of cellular mechanisms; however, mechanisms that regulate L-VGCC channel density and subcellular compartmentalization are understudied.

Executive function mediates age-related variation in social integration in female vervet monkeys (Chlorocebus sabaeus).

In humans, social participation and integration wane with advanced age, a pattern hypothesized to stem from cognitive or physical decrements. Similar age-related decreases in social participation have been observed in several nonhuman primate species. Here, we investigated cross-sectional age-related associations between social interactions, activity patterns, and cognitive function in 25 group-living female vervets (a.

Differential effects of western versus mediterranean diets and psychosocial stress on ovarian function in female monkeys (Macaca fascicularis).

Ovarian dysfunction increases risk for chronic diseases of aging including cardiovascular disease, depression, cognitive impairment, as well as bone and muscle loss which promote frailty. Psychosocial stress can disrupt ovarian function, and recent observations suggest that consumption of a Western Diet may also. Determination of causal relationships among diet, psychosocial stress, and ovarian physiology is difficult in humans.

Transcriptional profiles in olfactory pathway-associated brain regions of African green monkeys: Associations with age and Alzheimer's disease neuropathology.

Introduction: Olfactory impairment in older individuals is associated with an increased risk of Alzheimer's disease (AD). Characterization of age versus neuropathology-associated changes in the brain olfactory pathway may elucidate processes underlying early AD pathogenesis. Here, we report age versus AD neuropathology-associated differential transcription in four brain regions in the olfactory pathway of 10 female African green monkeys (vervet, ), a well-described model of early AD-like neuropathology.

Early Alzheimer's disease-like reductions in gray matter and cognitive function with aging in nonhuman primates.

Introduction: Age-related neuropathology associated with sporadic Alzheimer's disease (AD) often develops well before the onset of symptoms. Given AD's long preclinical period, translational models are needed to identify early signatures of pathological decline.

Methods: Using structural magnetic resonance imaging and cognitive assessments, we examined the relationships among age, cognitive performance, and neuroanatomy in 48 vervet monkeys () ranging from young adults to very old.

Dabigatran reduces thrombin-induced neuroinflammation and AD markers in vitro: Therapeutic relevance for Alzheimer's disease.

Background: Vascular risk factors such as atherosclerosis, diabetes, and elevated homocysteine levels are strongly correlated with onset of Alzheimer's disease (AD). Emerging evidence indicates that blood coagulation protein thrombin is associated with vascular and non-vascular risk factors of AD. Here, we examined the effect of thrombin and its direct inhibitor dabigatran on key mediators of neuro-inflammation and AD pathology in the retinoic acid (RA)-differentiated human neuroblastoma cell line SH-SY5Y.

Aging-related Alzheimer's disease-like neuropathology and functional decline in captive vervet monkeys (Chlorocebus aethiops sabaeus).

Age-related neurodegeneration characteristic of late-onset Alzheimer's disease (LOAD) begins in middle age, well before symptoms. Translational models to identify modifiable risk factors are needed to understand etiology and identify therapeutic targets. Here, we outline the evidence supporting the vervet monkey (Chlorocebus aethiops sabaeus) as a model of aging-related AD-like neuropathology and associated phenotypes including cognitive function, physical function, glucose handling, intestinal physiology, and CSF, blood, and neuroimaging biomarkers.

Temporal emergence of age-associated changes in cognitive and physical function in vervets (Chlorocebus aethiops sabaeus).

Dual declines in gait speed and cognitive performance are associated with increased risk of developing dementia. Characterizing the patterns of such impairments therefore is paramount to distinguishing healthy from pathological aging. Nonhuman primates such as vervet/African green monkeys (Chlorocebus aethiops sabaeus) are important models of human neurocognitive aging, yet the trajectory of dual decline has not been characterized.

Differentiating among stages of cognitive impairment in aging: Version 3 of the Uniform Data Set (UDS) neuropsychological test battery and MoCA index scores.

Introduction: Federally funded Alzheimer's Disease Centers in the United States have been using a standardized neuropsychological test battery as part of the National Alzheimer's Coordinating Center Uniform Data Set (UDS) since 2005. Version 3 (V3) of the UDS replaced the previous version (V2) in 2015. We compared V2 and V3 neuropsychological tests with respect to their ability to distinguish among the Clinical Dementia Rating (CDR) global scores of 0, 0.

Diet, psychosocial stress, and Alzheimer's disease-related neuroanatomy in female nonhuman primates.

Introduction: Associations between diet, psychosocial stress, and neurodegenerative disease, including Alzheimer's disease (AD), have been reported, but causal relationships are difficult to determine in human studies.

Methods: We used structural magnetic resonance imaging in a well-validated non-human primate model of AD-like neuropathology to examine the longitudinal effects of diet (Mediterranean vs Western) and social subordination stress on brain anatomy, including global volumes, cortical thicknesses and volumes, and 20 individual regions of interest (ROIs).

Results: Western diet resulted in greater cortical thicknesses, total brain volumes, and gray matter, and diminished cerebrospinal fluid and white matter volumes.

Expanded Demographic Norms for Version 3 of the Alzheimer Disease Centers' Neuropsychological Test Battery in the Uniform Data Set.

Background: Norms for the Uniform Data Set Version 3 Neuropsychological Battery are available for cognitively normal individuals based on age, education, and sex; however, these norms do not include race. We provide expanded norms for African Americans and whites.

Methods: Data from 32 Alzheimer's Disease Centers (ADCs) and ADC affiliated cohorts with global Clinical Dementia Rating Scale (CDR) Dementia Staging Instrument scores of 0 were included.