Development of amyloid burden in African Green monkeys

Abstract

The vervet is an old world monkey increasingly being used as a model for human diseases. In addition to plaques and tangles, an additional hallmark of Alzheimer’s disease is damage to neurons that synthesize noradrenaline (NA). We characterized amyloid burden in the posterior temporal lobe of young and aged vervets, and compared that to changes in NA levels and astrocyte activation. Total Aβ40 and Aβ42 levels were increased in the aged group, as were numbers of amyloid plaques detected using antibody 6E10. Low levels of Aβ42 were detected in 1 of 5 younger animals, although diffusely stained plaques were observed in 4 of these. Increased GFAP staining and mRNA levels were significantly correlated with increased age, as were cortical NA levels. Levels of Aβ42 and Aβ40, and the number of 6E10+ plaques, were correlated with NA levels. Interestingly mRNA levels of glial derived neurotrophic factor, important for noradrenergic neuronal survival, were reduced with age. These findings suggest that amyloid pathology in aged vervets is associated with astrocyte activation and higher NA levels.

Neurodegenerative disease biomarkers Aβ1–40, Aβ1–42, tau, and p‐tau181 in the vervet monkey cerebrospinal fluid: Relation to normal aging, genetic influences, and cerebral amyloid angiopathy

“…Here, we found that reductions in global measures of brain size (such as cerebral volume and total brain surface area) were associated with reduced CSF Aβ 1–40 and elevated CSF p‐tau 181 . Taken together with previous observations of age‐related amyloid plaques in the vervet (Kalinin et al., ; Lemere et al., ), the relationships with Aβ 1–40 and p‐tau 181 are consistent with a scenario of age‐related accumulation of amyloid plaques (in parenchyma and/or vasculature) corresponding to cerebral atrophy in the vervet. Though previous studies have found limited phospho‐tau immunoreactivity and few neurofibrillary tangles in the vervet brain (Lemere et al., ), the fact that elevations in p‐tau 181 levels in CSF are also correlated with changes in brain morphometry suggest that tau pathology may also play a role.…”

“…Nonhuman primates, unlike most other model organisms (e.g. mice and rats), are known to develop age-related amyloid pathology similar to that of Alzheimer's disease (AD) in humans (Kalinin et al, 2013;Ndung'u et al, 2012;Podlisny, Tolan, & Selkoe, 1991;Rosen et al, 2008;Toledano, Álvarez, López-Rodríguez, Toledano-Díaz, & Fernández-Verdecia, 2014), and have complex behavioral phenotypes closer to that in humans than other species could achieve. AD-related genes, such as those encoding β-amyloid (Aβ, APP) and tau (MAPT), are also highly similar (Holzer, Craxton, Jakes, Arendt, & Goedert, 2004;Podlisny et al, 1991).…”

Alzheimer’s disease: experimental models and reality

“…A limited number of studies have also been done examining AD associated neuropathology in vervets. Vervets live to approximately 30 years in captivity and have evidence of Aβ deposition, gliosis and neuronal dystrophy with age [72, 88, 89]. Amyloid deposition is first observed at approximately 15 years, and appears first in the vasculature prior to parenchymal plaques.…”

Pair housing of Vervets/African Green Monkeys for biomedical research

“…Vervets are relatively abundant, are not carriers of Herpes B virus, are easy to handle, and are less expensive than macaques [Baulu et al, ; Jasinska et al, ]. Vervets have been used in a wide variety of research areas including brain imaging [Fears et al, ; Woods et al, ], obesity and diabetes [Cann et al, ; Kavanagh et al, ], Alzheimer's disease [Kalinin et al, ; Lemere et al, ]; pharmacology/cognition [Groman et al, ; James et al, ; Melega et al, , ], immunology [Pandrea et al, ; Zahn et al, ], and genetics [Freimer et al, ; Jasinska et al, , ; Voruganti et al, ].…”