Senile plaques in aged squirrel monkeys

Walker, Lary C.; Kitt, Cheryl A.; Schwam, Elias; Buckwald, Beth; Garcia, F. G.; Sepinwall, Jerry; Price, Donald L.

doi:10.1016/0197-4580(87)90067-4

Cited by 86 publications

(29 citation statements)

References 24 publications

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“…) . Similar changes have been observed in aged monkeys, including squirrel monkey (13,14) and macaques (15)(16)(17)(18)(19)(20)(21), as well as in aged dog (22) and polar bear (23), and homology of APP in cynomolgus monkey and human has been demonstrated (24). Senile plaques have also been described in two aged mules (25), but neither plaques nor tangles were seen in three aged elephants (26).…”

mentioning

confidence: 56%

Neuropathology and apolipoprotein E profile of aged chimpanzees: implications for Alzheimer disease.

Gearing

Rebeck

Hyman

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

165

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It might be expected that great apes, because of their genetic similarity to humans (1-3), would be the most appropriate models for the study of the neuropathological changes seen in the brain in aging and Alzheimer disease (AD). These changes include senile plaques (extracellular aggregates of amyloid, often surrounded by degenerating neuronal processes), neurofibrillary tangles [intraneuronal cytoplasmic aggregates of paired helical filaments composed of abnormally phosphorylated microtubule-associated protein, tau (4-7)], and vascular amyloid deposition involving meningeal and cortical blood vessels. The amyloid in plaques and blood vessels is composed primarily of the amyloid a-protein (,B/A4), which is cleaved from the larger amyloid precursor protein (APP) (8-10).Given the relative rarity ofgreat apes in captivity combined with their long fife-spans (=w50-60 yr in captivity), studies of age-related changes in the brains ofthese primates have been extremely rare. Senile plaques and vascular amyloid have been described in a 46-yr-old orangutan (11), and vascular amyloid was noted in a 56-yr-old chimpanzee (these observations were made on a portion offrontal lobe from the brain of the same 56-yr-old chimpanzee included in the present study; ref. (28-31). Thus, the combination of senile plaques, vascular amyloid, and neurofibrillary tangles observed in AD has not yet been described in any animal species.Molecular studies suggest that, of the great apes, chimpanzees are most closely related to humans (1-3). Chimpanzees rarely survive past the age of 35 yr in the wild but may live well into the sixth decade in captivity (32). Gamma, the 59-yr-old chimpanzee in our study, was the oldest known chimpanzee. In contrast, the maximum ifMe-span for rhesus monkeys has been estimated at just under 40 yr, with aging in rhesus monkeys estimated to occur at about three times the rate in humans (12,(32)(33)(34)(35). We had the opportunity to examine the brains of three aged chimpanzees (Pan troglodytes), two females aged 56 (Bula) and 59 yr (Gamma) and a male (Frans) aged 45 yr, and to compare the changes observed with those seen in the brains of four elderly rhesus monkeys (Macaca mulatta), aged 20, 21, 29, and 30 yr, and in the brains of individuals with AD.

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mentioning

confidence: 56%

Neuropathology and apolipoprotein E profile of aged chimpanzees: implications for Alzheimer disease.

Gearing

Rebeck

Hyman

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

165

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“…The need for an animal model for AD is particularly pressing considering the number of people who are suffering or will suffer from this disease. Amyloid deposits similar to those observed in human brains have been described in aged non-human primates (Dayan, 1971;Kitt et al, 1984Kitt et al, , 1985Price et al, 1985;Struble et al, 1985;Walker et al, 1986Walker et al, , 1987. Numerous plaques were also observed in the brains of aged bears (Cork et al, 1988).…”

Section: Introductionmentioning

confidence: 62%

Aged dogs: an animal model to study beta-protein amyloidogenesis

Wı́sniewski

Węgiel

Moryś

et al. 1990

Key Topics in Brain Research

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SummaryThe morphology, incidence and distribution of plaques and diffuse amyloid deposits in the brains of seven old dogs (18.5-26.5 years of age) were examined on tissue sections immunocytochemically stained with two monoclonal antibodies to two distinct epitopes of the beta-protein. Amyloid deposits were found in all seven brains examined. Amyloid occurred in three morphological forms: 1. focal amyloid deposits (plaques), 2. large diffuse amyloid deposits and 3. amyloid angiopathy. The number of these deposits was comparable to the numbers of all three types of amyloid deposits seen in the brains of people with Alzheimer's disease. The number and type of morphological forms of the amyloid deposits depends on topography and the age of the animals. The number of plaques was highest in the brains of the animals 18.5-21 years of age. The oldest animals (21.5, 24 and 26.5 years of age) had a smaller number of amyloid deposits. With age, the number of plaques decreased in superficial layers of the cerebral cortex (II-III) and increased in the deeper layers (IV-VI). In the oldest animals, diffuse amyloid deposits in the deeper layers of the cortex predominated. Our studies suggest that the frequency and the extent of amyloid deposits in the brains of aged dogs are much wider than so far appreciated. It thus appears that aged dogs may be suitable as an animal model for the study of pathomechanisms involved in beta-protein amyloidogenesis.

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“…Studies of rhesus monkeys yielded the first experimental evidence of the varied and complex neuritic composition of senile plaques, and have helped to illuminate the nature of senile plaques and Ab in brain [45,46]. Squirrel monkeys are now an established animal model of CAA [47,48] and have been employed in studies of the genetic, biochemical and physiological factors that foster amyloid angiopathy [10,32,45,[49][50][51][52][53][54][55]. Similarities in age-associated neuropathology, in conjunction with the immunological and vascular commonalities of human and nonhuman primates, indicate that rhesus monkeys and squirrel monkeys are ideal for rigorously testing the safety and efficacy of Ab immunotherapy.…”

Section: Cerebral B-amyloid Angiopathymentioning

confidence: 99%