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

Abstract

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. This review provides the most comprehensive multisystem description of aging in vervets to date. This review synthesizes a large body of evidence that suggests that aging vervets exhibit a coordinated suite of traits consistent with early AD and provide a powerful, naturally occurring model for LOAD. Notably, relationships are identified between AD-like neuropathology and modifiable risk factors. Gaps in knowledge and key limitations are provided to shape future studies to illuminate mechanisms underlying divergent neurocognitive aging trajectories and to develop interventions that increase resilience to aging-associated chronic disease, particularly, LOAD.

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

“…(Chaudron, Pifferi, & Aujard, 2021), d (Perret, 1997), e (Hämäläinen et al, 2014), f (Weigl, 2005), g (Gary et al, 2019), h (Abbott & Hearn, 1978), i (Ross, 2019), j (Nishijima et al, 2012;Weigl, 2005), k (Abbott et al, 2003), l (Maclean et al, 2000), m (Philippens et al, 2016), n (Ridley et al, 2006), o (Jorgensen, 2021) & Jorgensen pers. comm., p (Atkins et al, 2014), q (Schmitt et al, 2018), r (Cramer et al, 2018), s (Kavanagh et al, 2019) t (Frye et al, 2021), u (van Wagenen, 1952), v (Plant, 2005), w (Tigges, Gordon, McClure, Hall, & Peters, 1988), x (Upright & Baxter, 2021), y (Stonebarger et al, 2020), z…”

“…Within the comparative perspective of this Special Issue, the authors have addressed various aspects of the aging phenotype in wellcharacterized and emerging NHP models, ranging from prosimians to hominids, including: gray mouse lemurs (Chaudron et al 2021), common marmosets (Rothwell et al, 2021), vervet/African green monkeys (Frye et al, 2021), three macaque species: rhesus (Arnsten et al, 2021;Upright & Baxter, 2021), cynomolgus (Darusman et al, 2021), and Barbary (Rathke & Fischer, 2021); and chimpanzees (Mulholland et al, 2021). Four main themes emerge from this collection.…”

“…Using Volumetric Based Morphometry in chimpanzees who were cognitively characterized, they show that successful agers have greater gray matter volume in many brain regions compared to apes who underperform for their age, and that these differences concern regions that typically decline with age. Frye et al (2021) also provide evidence that vervet monkeys recapitulate many of the features of early AD pathophysiology. Finally, the review by Freire‐Cobo et al (2021) offers a much‐needed inventory of the age‐related cellular changes that occur with normal and pathological aging across primate species.…”

“…References: a (Freire‐Cobo et al, 2021), b (Languille et al, 2012), c (Chaudron, Pifferi, & Aujard, 2021), d (Perret, 1997), e (Hämäläinen et al, 2014), f (Weigl, 2005), g (Gary et al, 2019), h (Abbott & Hearn, 1978), i (Ross, 2019), j (Nishijima et al, 2012; Weigl, 2005), k (Abbott et al, 2003), l (Maclean et al, 2000), m (Philippens et al, 2016), n (Ridley et al, 2006), o (Jorgensen, 2021) & Jorgensen pers. comm., p (Atkins et al, 2014), q (Schmitt et al, 2018), r (Cramer et al, 2018), s (Kavanagh et al, 2019) t (Frye et al, 2021), u (van Wagenen, 1952), v (Plant, 2005), w (Tigges, Gordon, McClure, Hall, & Peters, 1988), x (Upright & Baxter, 2021), y (Stonebarger et al, 2020), z (Walker, 1995), aa (Beckman et al, 2019a), bb (Beckman et al, 2021), cc (Fa, 1989), dd(Luetjens & Weinbauer, 2012), ee (Van Esch et al, 2008), ff (Kavanagh et al, 2005), gg (Darusman et al, 2014), hh (Forny‐Germano et al, 2014), ii (Fooden, 2007), jj (Paul, Kuester, & Podzuweit, 1993; Weigl, 2005), kk (Rathke & Fischer, 2021), ll (Leigh & Shea, 1995), mm (Muller et al, 2020), nn (Dyke et al, 1995), oo (Lacreuse et al, 2008), pp (Hopkins et al, 2020), qq (Walpole et al, 2012), rr (Hochberg & Konner, 2020), ss (Arias et al, 2020), tt (Robine & Allard, 1999), uu (Gold, 2011), vv(Shoven, 2007).…”

Integrated Omics Analysis Reveals Sirtuin Signaling is Central to Hepatic Response to a High Fructose Diet

“…The vervet monkey ( Chlorocebus aethiops sabaeus ) is a model for multiple human complex diseases including neurodegenerative disease (11), Alzheimer’s disease (12–15), diabetes, obesity and metabolism (16–18) and cardiovascular disease (19, 20) among others. Due to the high degree of genomic (21–23), physiologic and metabolic conservation between vervets and humans, results in vervets are translatable to understanding human health and disease.…”