Like humans, primates have life-spans of multi decades. Captive rhesus monkeys can live into the decades. Monkeys older than 20 years are equivalent of human 60 to 70 years old (Bowden and Williams 1984, Adv. Vet. Sci. Comp. Med. 28:305). As they grow older, humans and primates experience many of the same age-related changes in anatomy, physiology, mental function, and behavior . Aged rhesus monkeys – those older than 23 years of age – have cognitive and memory deficits and develop senile plaques with neuritis derived from cholinergic and other neurotransmitter system  (Price et al., Brain Pathol. 1991, 1:287-296).

Alzheimer’s disease is primarily a disease of cortical derangement and cobnitive impairment. The well-developed cerebral cortex of primates makes these animals extremely valuable for research on Alzheimer’s disease.

There are 50 rhesus monkeys over 20 years old in our China facility. In aged monkey brains, we can find spontaneous senile plaque formation: one of the major histopathological features in Alzheimer’s disease. Thus aged monkey is considered as an useful animal model for Alzheimer’s disease and other aging-causative neurodegenerative disorders.

-     Physical and behavioral changes that accompany aging are recorded and scaled: reversal learning, increased stereotyping of spontaneous behavior, increased reaction time, changes in sensory processing, and reduced long-term memory, according to Bartus methods (Bartus et al. 1983, Psychopharmacol. Bull., 19:168) including food reward scale and visual recognition memory task, etc.

-     Immunohistochemistry reaction in  deposits (senile plaques) significantly increasedbthe brain sections showed A with age.

-      Biochemistry analysis for measuring level of acetylcholine (Ach), a neurotransmitter decreased in Alzheimer’s disease and other monoamines such as catecholamine, GABA, serotonin, as well as neuroactive peptides.

AD Rhesus Model - Transections of the fimbria-fornix

One of the neuropathological changes that has received intensive evaluation by scientists is the cholinergic deficit in the neocortex and the forebrain limbic system. Alzheimer’s patients lose 75-85% of their neurons in the nucleus basalis of Meynert (nbM). The transactions of the fimbria-fornix in monkey brain can induce retrograde degeneration of neurons in the basal forebrain cholinergic system including both nbM and medial septum, this model has been suggested to be alterations of older individuals (Price et al., Brain Pathol. 1991, 1:287-296).

-          stereotaxic sugery – Axotomy

-          Behavioral recording and analysis: declines in performance on cognitive and memory tasks according to Bartus methods (Bartus et al. 1983, Psychopharmacol. Bull., 19:168).

-          Neuropathologic examination (degenerative changes in neurons, abnormal axons and neuritis, deposits of amyloid in senile plaques, etc.)

 Biochemical analysis of cholinergic neurotransmitters in the brain tissue or in the CSF.