Distribution, progression and chemical composition of cortical amyloid-β deposits in aged rhesus monkeys: similarities to the human
Abstract
A comprehensive investigation of the incidence, distribution, progression and chemical composition of Abeta deposits in the brains of two young (5 years) and seven aged (25-30 years) rhesus monkeys was conducted to determine the similarity of this phenomenon to that in the human. The brains of the young rhesus were devoid of Abeta deposits. In contrast, Abeta deposits were observed within the cerebral cortex of all aged animals. In animals with mild Abeta burden, deposits were observed primarily in association cortical zones. In animals with moderate Abeta burden, many paralimbic cortical zones also contained Abeta deposits. Finally, in an animal with a heavy burden of Abeta, core limbic cortical zones were also involved. The primary sensory and motor cortices were relatively free of Abeta deposits. A higher proportion of plaques contained Abeta40 as compared with Abeta42. Abeta deposits contained a number of other constituents. Cholinesterases were present in nearly 50% of plaques and displayed the exact same biochemical characteristics as those in the human. Nearly 20% of Abeta deposits also contained apolipoprotein E and a smaller proportion contained heparin sulfate proteoglycans and alpha1-anti-chymotrypsin. The latter three chemicals were present in many compact plaques. These results indicate that the distribution, progression and chemical composition of plaques in the aged rhesus monkey display many similarities to those observed in the aged human and Alzheimer's disease. Therefore, despite some differences from the human, the aged rhesus may be a good model for studies of the pathological effects of Abeta in the primate brain.
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The majority of plaques in rhesus monkeys are diffuse; only approximately 20% contained fibrillar Aβ.
“The majority of plaques are diffuse; only approximately 20% contained fibrillar Aβ [134, 146].”
From Alzheimer's disease: experimental models and reality (2017) · cites this paper as [134]
Plaques are typically found in rhesus monkeys older than 25 years and have a similar distribution to humans, with more present in the cortex than the hippocampus.
“Plaques are typically found in rhesus monkeys that are older than 25 years and they have a similar distribution that that observed in humans; more being present in the cortex than the hippocampus [54, 56, 96, 134, 146, 150, 164, 165].”
From Alzheimer's disease: experimental models and reality (2017) · cites this paper as [134]
Cites
Correlative Memory Deficits, Aβ Elevation, and Amyloid Plaques in Transgenic Mice
Hsiao, K., Chapman, P., Nilsen, S., Eckman, C., Harigaya, Y., Younkin, S., Yang, F., & Cole, G. (1996) · Science · doi:10.1126/science.274.5284.99 · Cited by 4,210 · see citing works
Association of apolipoprotein E allele ϵ4 with late‐onset familial and sporadic Alzheimer's disease
Saunders, A. M., Strittmatter, W. J., Schmechel, D., St. George-Hyslop, P. H., Pericak-Vance, M. A., Joo, S. H., Rosi, B. L., Gusella, J. F., Crapper-MacLachlan, D. R., Alberts, M. J., et al. (1993) · Neurology · doi:10.1212/wnl.43.8.1467 · Cited by 3,786 · see citing works
Alzheimer-type neuropathology in transgenic mice overexpressing V717F β-amyloid precursor protein
Games, D., Adams, D., Alessandrini, R., Barbour, R., Borthelette, P., Blackwell, C., Carr, T., Clemens, J., Donaldson, T., Gillespie, F., et al. (1995) · Nature · doi:10.1038/373523a0 · Cited by 2,516 · see citing works
Iwatsubo, T., Odaka, A., Suzuki, N., Mizusawa, H., Nukina, N., & Ihara, Y. (1994) · Neuron · doi:10.1016/0896-6273(94)90458-8 · Cited by 1,774 · see citing works
Two amyloid precursor protein transgenic mouse models with Alzheimer disease-like pathology
Sturchler-Pierrat, C., Abramowski, D., Duke, M., Wiederhold, K.-H., Mistl, C., Rothacher, S., Ledermann, B., Bürki, K., Frey, P., Paganetti, P. A., et al. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.24.13287 · Cited by 1,507 · see citing works
Arnold, S. E., Hyman, B. T., Flory, J., Damasio, A. R., & Van Hoesen, G. W. (1991) · Cerebral Cortex · doi:10.1093/cercor/1.1.103 · Cited by 1,380 · see citing works
Beta-amyloid neurotoxicity requires fibril formation and is inhibited by congo red.
Lorenzo, A., & Yankner, B. A. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.25.12243 · Cited by 1,324 · see citing works
Chartier-Harlin, M.-C., Crawford, F., Houlden, H., Warren, A., Hughes, D., Fidani, L., Goate, A., Rossor, M., Roques, P., Hardy, J., et al. (1991) · Nature · doi:10.1038/353844a0 · Cited by 1,214 · see citing works
Inestrosa, N. C., Alvarez, A. R., Pérez, C. A., Moreno, R. D., Vicente, M., Linker, C., Casanueva, O. I., Soto, C. A., & Garrido, J. (1996) · Neuron · doi:10.1016/s0896-6273(00)80108-7 · Cited by 1,107 · see citing works
Apolipoprotein E in sporadic Alzheimer's disease: Allelic variation and receptor interactions
William Rebeck, G., Reiter, J. S., Strickland, D. K., & Hyman, B. T. (1993) · Neuron · doi:10.1016/0896-6273(93)90070-8 · Cited by 1,107 · see citing works
Mechanisms of Neuronal Degeneration in Alzheimer's Disease
Yankner, B. A. (1996) · Neuron · doi:10.1016/s0896-6273(00)80115-4 · Cited by 947 · see citing works
Price, J. L., Davis, P. B., Morris, J. C., & White, D. L. (1991) · Neurobiology of Aging · doi:10.1016/0197-4580(91)90006-6 · Cited by 818 · see citing works
The Pathogenesis of Senile Plaques
DICKSON, D. W. (1997) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/00005072-199704000-00001 · Cited by 753 · see citing works
Hendriks, L., van Duijn, C. M., Cras, P. P., Cruts, M., Hul, W. V., van Harskamp, F., Warren, A., McInnis, M. G., Antonarakis, S. E., Martin, J., et al. (1992) · Nature Genetics · doi:10.1038/ng0692-218 · Cited by 735 · see citing works
Arriagada, P. V., Marzloff, K., & Hyman, B. T. (1992) · Neurology · doi:10.1212/wnl.42.9.1681 · Cited by 638 · see citing works
Selkoe, D. J. (2000) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2000.tb05554.x · Cited by 627 · see citing works
Ellis, R. J., Olichney, J. M., Thal, L. J., Mirra, S. S., Morris, J. C., Beekly, D., & Heyman, A. (1996) · Neurology · doi:10.1212/wnl.46.6.1592 · Cited by 561 · see citing works
An in vivo model for the neurodegenerative effects of beta amyloid and protection by substance P.
Kowall, N. W., Beal, M. F., Busciglio, J. A., Duffy, L. K., & Yankner, B. A. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.16.7247 · Cited by 525 · see citing works
Aging renders the brain vulnerable to amyloid β-protein neurotoxicity
Guela, C., Wu, C.-K., Saroff, D., Lorenzo, A., Yuan, M., & Yankner, B. A. (1998) · Nature Medicine · doi:10.1038/nm0798-827 · Cited by 520 · see citing works
Self-citationNeuron loss in APP transgenic mice
Calhoun, M. E., Wiederhold, K.-H., Abramowski, D., Phinney, A. L., Probst, A., Sturchler-Pierrat, C., Staufenbiel, M., Sommer, B., & Jucker, M. (1998) · Nature · doi:10.1038/27351 · Cited by 502 · see citing works
Irizarry, M. C., Soriano, F., McNamara, M., Page, K. J., Schenk, D., Games, D., & Hyman, B. T. (1997) · The Journal of Neuroscience · doi:10.1523/jneurosci.17-18-07053.1997 · Cited by 497 · see citing works
Berg, L., McKeel, D. W., Miller, J. P., Baty, J., & Morris, J. C. (1993) · Archives of Neurology · doi:10.1001/archneur.1993.00540040011008 · Cited by 257 · see citing works
Levey, A. I., Bolam, J. P., Rye, D. B., Hallanger, A. E., Demuth, R., Mesulam, M. M., & Wainer, B. (1986) · Journal of Histochemistry & Cytochemistry · doi:10.1177/34.11.2430010 · Cited by 234 · see citing works
Senile plaques in cortex of aged normal monkeys.
Struble, R., Price, D. L., & Cork, L. (1985) · Brain Research · doi:10.1016/0006-8993(85)91298-3 · Cited by 182 · see citing works
Special properties of cholinesterases in the cerebral cortex of Alzheimer's disease
Geula, C., & Mesulam, M. M. (1989) · Brain Research · doi:10.1016/0006-8993(89)90419-8 · Cited by 137 · see citing works
Self-citationEmre, M., Geula, C., Ransil, B., & Mesulam, M. M. (1992) · Neurobiology of Aging · doi:10.1016/0197-4580(92)90055-3 · Cited by 125 · see citing works
Self-citationAβ40 is a major form of β-amyloid in nonhuman primates
Gearing, M., Tigges, J., Mori, H., & Mirra, S. S. (1996) · Neurobiology of Aging · doi:10.1016/s0197-4580(96)00164-9 · Cited by 114 · see citing works
Development of senile plaques. Relationships of neuronal abnormalities and amyloid deposits.
Cork, L. C., Masters, C. L., Beyreuther, K. T., & Price, D. L. (1990) · Europe PMC (PubMed Central) · Cited by 112 · see citing works
Relationship between plaques, tangles, and loss of cortical cholinergic fibers in alzheimer disease
Geula, C., Mesulam, M. M., Saroff, D. M., & Wu, C.-K. (1998) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/00005072-199801000-00008 · Cited by 102 · cited 1× · see citing works
“Previous reports from our laboratory [ 17 ] and those of others [2, 4] have shown a similar distribution of Aβ deposits in AD. Thus, the greatest number of cortical Aβ deposits in the AD brain are found within association cortical areas, followed by paralimbic and limbic zones, with the lowest density found within pri…”
Self-citationLack of correlation between plaque burden and cognition in the aged monkey
Sloane, J. A., Pietropaolo, M., Rosene, D. L., Moss, M. B., Peters, A., Kemper, T. L., & Abraham, C. R. (1997) · Acta Neuropathologica · doi:10.1007/s004010050735 · Cited by 101 · see citing works
Poduri, A., Gearing, M., Rebeck, G. W., Mirra, S. S., Tigges, J., & Hyman, B. T. (1994) · PubMed Central · Cited by 97 · see citing works
Mak, K., Yang, F., Vinters, H. V., Frautschy, S. A., & Cole, G. M. (1994) · Brain Research · doi:10.1016/0006-8993(94)91725-6 · Cited by 80 · see citing works
Cerebral amyloid angiopathy and plaques, and visceral amyloidosis in aged macaques
Uno, H., Alsum, P. B., Dong, S., Richardson, R., Zimbric, M. L., Thieme, C. S., & Houser†, W. D. (1996) · Neurobiology of Aging · doi:10.1016/0197-4580(95)02063-2 · Cited by 72 · see citing works
Wright, C. I., Guela, C., & Mesulam, M. ‐. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.2.683 · Cited by 72 · see citing works
George, S. T., & Balasubramanian, A. S. (1980) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1980.tb04967.x · Cited by 67 · see citing works
Apolipoprotein E-immunoreactivity in aged rhesus monkey cortex: Colocalization with amyloid plaques
Mufson, E. J., Benzing, W. C., Cole, G. M., Wang, H., Emerich, D. F., Sladek, J. R., Morrison, J. H., & Kordower, J. H. (1994) · Neurobiology of Aging · doi:10.1016/0197-4580(94)00064-6 · Cited by 58 · see citing works
The cytoarchitectonic distribution of senile plaques in three aged monkeys
Heilbroner, P. L., & Kemper, T. L. (1990) · Acta Neuropathologica · doi:10.1007/bf00662638 · Cited by 54 · see citing works
Acetylcholinesterase activity in senile plaques of aged macaques
Struble, R. G., Hedreen, J. C., Cork, L. C., & Price, D. L. (1984) · Neurobiology of Aging · doi:10.1016/0197-4580(84)90062-9 · Cited by 45 · see citing works
11. Molecular genetics of Alzheimer's disease
Hardy, J., Owen, M. J., Goate, A., James, L., Haynes, A. R., Williamson, R., Roques, P. K., Rossor, M. N., & Mullan, M. J. (1989) · Springer eBooks · doi:10.1007/978-1-4613-0513-2_3 · Cited by 44 · see citing works
Härtig, W., Brückner, G., Schmidt, C., Brauer, K., Bodewitz, G., Turner, J. D., & Bigl, V. (1997) · Brain Research · doi:10.1016/s0006-8993(96)01423-0 · Cited by 36 · see citing works
Iizuka, T., Shoji, M., Harigaya, Y., Kawarabayashi, T., Watanabe, M., Kanai, M., & Hirai, S. (1995) · Brain Research · doi:10.1016/0006-8993(95)01163-2 · Cited by 33 · see citing works
Age-Related Cognitive Decline in the Rhesus Monkey
Moss, M. B., Killiany, R., & Herndon, J. G. (1999) · Cerebral cortex · doi:10.1007/978-1-4615-4885-0_2 · Cited by 31 · see citing works
Wright, C. I., Geula, C., & Mesulam, M. M. (1993) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1993.tb23029.x · Cited by 28 · see citing works
Self-citationTemplate atlas of the primate brain
Martin, R. F., & Bowden, D. M. (1996) · Medical Entomology and Zoology · Cited by 24 · see citing works
Pathological Diagnosis of Alzheimer’s Disease
Geula, C. (2000) · Humana Press eBooks · doi:10.1007/978-1-59259-005-6_3 · Cited by 11 · see citing works
Self-citationSchätz, C. R., Geula, C., Morecraft, R. J., et al. (1992) · Journal of Histochemistry & Cytochemistry · doi:10.1177/40.3.1552180 · Cited by 11 · see citing works
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Alzheimer's disease: experimental models and reality
Drummond, E., & Wisniewski, T. (2017) · Acta Neuropathologica · doi:10.1007/s00401-016-1662-x · Cited by 810 · see citing works
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Heuer, E., F. Rosen, R., Cintron, A., & C. Walker, L. (2012) · Current Pharmaceutical Design · doi:10.2174/138161212799315885 · Cited by 169 · see citing works
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- Authors
- Sani, S., Traul, D., Klink, A., Niaraki, N., Gonzalo-Ruiz, A., Wu, C.-K., & Geula, C.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Geula, Changiz
- Venue
- Acta Neuropathologica
- Published
- 2003-02
- Volume
- 105
- Issue
- 2
- Pages
- 145-156
- ISSN
- 0001-6322 (ISSN-L)
- 1432-0533
- OpenAlex
- W1483033914
- Cited by
- 83
- References
- 46
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 8 · 2023: 2 · 2022: 8 · 2021: 5 · 2020: 2 · 2019: 2 · 2018: 2 · 2016: 4 · 2015: 1 · 2014: 5 · 2013: 1 · 2012: 5
- FWCI
- 1.34
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Acta Neuropathologica (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- amyloid-beta deposition, rhesus monkeys, aging, Alzheimer's disease model, cholinesterase, apolipoprotein E, heparan sulfate proteoglycans, cerebral cortex, primate brain
- MeSH terms
- Age Factors, Aging, Animals, Apolipoproteins E, Brain Chemistry, Brain Diseases, Cholinesterases, Chymotrypsin, Disease Models, Animal, Heparin, Humans, Immunohistochemistry, Proteoglycans, Amyloid beta-Peptides, Plaque, Amyloid
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