Lessons from the analysis of nonhuman primates for understanding human aging and neurodegenerative diseases

Animal models are necessary tools for solving the most serious challenges facing medical research. In aging and neurodegenerative disease studies, rodents occupy a place of choice. However, the most challenging questions about longevity, the complexity and functioning of brain networks or social intelligence can almost only be investigated in nonhuman primates. Beside the fact that their brain structure is much closer to that of humans, they develop highly complex cognitive strategies and they are visually-oriented like humans. For these reasons, they deserve consideration, although their management and care are more complicated and the related costs much higher. Despite these caveats, considerable scientific advances have been possible using nonhuman primates. This review concisely summarizes their role in the study of aging and of the mechanisms involved in neurodegenerative disorders associated mainly with cognitive dysfunctions (Alzheimer's and prion diseases) or motor deficits (Parkinson's and related diseases).

[1]  E. Zimmermann,et al.  Touchscreen-Based Cognitive Tasks Reveal Age-Related Impairment in a Primate Aging Model, the Grey Mouse Lemur (Microcebus murinus) , 2014, PloS one.

[2]  D. Ingram,et al.  Overview of aging research using nonhuman primate models , 2012, AGE.

[3]  Weber Heinz.  CHAPTER 17 – Factors Affecting the Choice of Species , 2005 .

[4]  F. Mouthon,et al.  Risk of oral infection with bovine spongiform encephalopathy agent in primates , 2005, The Lancet.

[5]  L. Walker,et al.  The Age of Biosenescence and the Incidence of Cerebral β‐Amyloidosis in Aged Captive Rhesus Monkeys a , 1993, Annals of the New York Academy of Sciences.

[6]  Mark H. Tuszynski,et al.  Age-related cognitive deficits in rhesus monkeys mirror human deficits on an automated test battery , 2010, Neurobiology of Aging.

[7]  R. Passingham,et al.  Evolution of the primate prefrontal cortex , 2012 .

[8]  F. Checler,et al.  Immunohistochemical Analysis of Cerebral Cortical and Vascular Lesions in the Primate Microcebus murinus Reveal Distinct Amyloid β1–42 and β1–40 Immunoreactivity Profiles , 2000, Neurobiology of Disease.

[9]  N. Zawia,et al.  Enhanced taupathy and AD-like pathology in aged primate brains decades after infantile exposure to lead (Pb). , 2013, Neurotoxicology.

[10]  A. Fagan,et al.  Cerebral amyloid-beta protein accumulation with aging in cotton-top tamarins: a model of early Alzheimer's disease? , 2008, Rejuvenation research.

[11]  P. Schoenemann,et al.  Prefrontal white matter volume is disproportionately larger in humans than in other primates , 2005, Nature Neuroscience.

[12]  R. Motter,et al.  Immunization with amyloid-β attenuates Alzheimer-disease-like pathology in the PDAPP mouse , 1999, Nature.

[13]  V. Pantesco,et al.  Distinct Transcriptome Expression of the Temporal Cortex of the Primate Microcebus murinus during Brain Aging versus Alzheimer's Disease-Like Pathology , 2010, PloS one.

[14]  F. Gage,et al.  Age-associated neuronal atrophy occurs in the primate brain and is reversible by growth factor gene therapy. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[15]  C. Shively,et al.  Development of amyloid burden in African Green monkeys , 2013, Neurobiology of Aging.

[16]  J. Stone,et al.  The topography of primate retina: A study of the human, bushbaby, and new‐ and old‐world monkeys , 1981, The Journal of comparative neurology.

[17]  Nicole R. Zürcher,et al.  Performance of juvenile baboons on neuropsychological tests assessing associative learning, motivation and attention , 2010, Journal of Neuroscience Methods.

[18]  P. Fraser.  Prions and Prion-like Proteins , 2014, The Journal of Biological Chemistry.

[19]  S. Trouche,et al.  Antibody response and plasma Abeta1-40 levels in young Microcebus murinus primates immunized with Abeta1-42 and its derivatives. , 2009, Vaccine.

[20]  O. Blin,et al.  The grey mouse lemur: A non-human primate model for ageing studies , 2012, Ageing Research Reviews.

[21]  F. Aujard,et al.  Physical activity and balance performance as a function of age in a prosimian primate (Microcebus murinus) , 2003, Experimental Gerontology.

[22]  G. Weinbauer,et al.  Reproductive/Developmental Toxicity Assessment of Biopharmaceuticals in Nonhuman Primates , 2010 .

[23]  J. Call,et al.  Poor memory performance in aged cynomolgus monkeys with hippocampal atrophy, depletion of amyloid beta 1-42 and accumulation of tau proteins in cerebrospinal fluid. , 2014, In vivo.

[24]  A. Benabid,et al.  Discovery of high-frequency deep brain stimulation for treatment of Parkinson disease: 2014 Lasker Award. , 2014, JAMA.

[25]  S. Herculano‐Houzel.  Neuronal scaling rules for primate brains: the primate advantage. , 2012, Progress in brain research.

[26]  P. Luciw,et al.  Macaque Models of Human Infectious Disease , 2008, ILAR journal.

[27]  E. V. van Someren,et al.  Live to the rhythm, slave to the rhythm. , 2007, Sleep medicine reviews.

[28]  G. Weinbauer,et al.  Developmental and reproductive toxicology studies in nonhuman primates. , 2009, Birth defects research. Part B, Developmental and reproductive toxicology.

[29]  Giovanni Coppola,et al.  Tauopathy with paired helical filaments in an aged chimpanzee , 2008, The Journal of comparative neurology.

[30]  Steven N. Austad,et al.  Primate aging in the mammalian scheme: the puzzle of extreme variation in brain aging , 2011, AGE.

[31]  B. '. ’t Hart,et al.  The MPTP marmoset model of parkinsonism: a multi-purpose non-human primate model for neurodegenerative diseases. , 2010, Drug discovery today.

[32]  T. Prolla,et al.  Evolution of the Aging Brain Transcriptome and Synaptic Regulation , 2008, PloS one.

[33]  R. Passingham,et al.  The Neurobiology of the Prefrontal Cortex: Anatomy, Evolution, and the Origin of Insight , 2012 .

[34]  H. Bergman,et al.  Reversal of experimental parkinsonism by lesions of the subthalamic nucleus. , 1990, Science.

[35]  S. Austad,et al.  The development of small primate models for aging research. , 2011, ILAR journal.

[36]  H. Kennedy,et al.  Early Presymptomatic and Long-Term Changes of Rest Activity Cycles and Cognitive Behavior in a MPTP-Monkey Model of Parkinson's Disease , 2011, PloS one.

[37]  H. Nakayama,et al.  Histopathological studies of senile plaques and cerebral amyloidosis in cynomolgus monkeys , 1998, Journal of medical primatology.

[38]  L. Walker,et al.  Animal models of cerebral β-amyloid angiopathy , 1997, Brain Research Reviews.

[39]  S. Trouche,et al.  Amyloid beta immunization worsens iron deposits in the choroid plexus and cerebral microbleeds , 2013, Neurobiology of Aging.

[40]  S. Knauf,et al.  Respiratory Animal Models in the Common Marmoset (Callithrix jacchus) , 2014 .

[41]  M. Dhenain,et al.  Age-related cerebral atrophy in nonhuman primates predicts cognitive impairments , 2012, Neurobiology of Aging.

[42]  A. Holleschau,et al.  The effects of age on glutathione synthesis enzymes in lenses of Old World simians and prosimians. , 1992, Current eye research.

[43]  Y. Matsuura,et al.  Oral Transmission of L-Type Bovine Spongiform Encephalopathy Agent among Cattle , 2017, Emerging infectious diseases.

[44]  B. Dubois,et al.  Subacute meningoencephalitis in a subset of patients with AD after Aβ42 immunization , 2003, Neurology.

[45]  E. Heuer,et al.  Nonhuman primate models of Alzheimer-like cerebral proteopathy. , 2012, Current pharmaceutical design.

[46]  P. Liberski,et al.  Non-human primates in prion research. , 2012, Folia neuropathologica.

[47]  G. Weinbauer,et al.  Reproductive/developmental toxicity and immunotoxicity assessment in the nonhuman primate model. , 2003, Toxicology.

[48]  S. Picaud,et al.  Microcebus murinus retina: A new model to assess prion-related neurotoxicity in primates , 2010, Neurobiology of Disease.

[49]  E. Bézard,et al.  Microarray analysis of nonhuman primates: validation of experimental models in neurological disorders , 2003, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[50]  D. Dormont,et al.  Tissue distribution of bovine spongiform encephalopathy agent in primates after intravenous or oral infection , 2004, The Lancet.

[51]  N. M. Brooke,et al.  A molecular timescale for vertebrate evolution , 1998, Nature.

[52]  C. Cotman,et al.  Pyroglutamate-3 amyloid-β deposition in the brains of humans, non-human primates, canines, and Alzheimer disease-like transgenic mouse models. , 2013, The American journal of pathology.

[53]  Perspectives on the Non-Human Primate Touch-Screen Self Ordered Spatial Search Paradigm , 2012 .

[54]  Frank R. Ervin,et al.  Alzheimer's Disease Aβ Vaccine Reduces Central Nervous System Aβ Levels in a Non-Human Primate, the Caribbean Vervet , 2004 .

[55]  Thierry Wannier,et al.  Can experiments in nonhuman primates expedite the translation of treatments for spinal cord injury in humans? , 2007, Nature Medicine.

[56]  J. Kaas,et al.  Connectivity-driven white matter scaling and folding in primate cerebral cortex , 2010, Proceedings of the National Academy of Sciences.

[57]  A. Delacourte,et al.  Immunocytochemical characterization of Tau proteins during cerebral aging of the lemurian primate Microcebus murinus. , 1995, Comptes rendus de l'Academie des sciences. Serie III, Sciences de la vie.

[58]  K. Tyler,et al.  Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to nonhuman primates. , 1980, The Journal of infectious diseases.

[59]  G. Elder,et al.  Modeling human neurodegenerative diseases in transgenic systems , 2011, Human Genetics.

[60]  M. Perret.  Change in Photoperiodic Cycle Affects Life Span in a Prosimian Primate (Microcebus murinus , 1997, Journal of biological rhythms.

[61]  N. Mestre‐Francés,et al.  Oral Transmission of L-type Bovine Spongiform Encephalopathy in Primate Model , 2012, Emerging infectious diseases.

[62]  J. Goodall.  The Chimpanzees of Gombe: Patterns of Behavior , 1986 .

[63]  M. Nader,et al.  Environmental modulation of drug taking: Nonhuman primate models of cocaine abuse and PET neuroimaging , 2014, Neuropharmacology.

[64]  B Frangione,et al.  Immunization with a nontoxic/nonfibrillar amyloid-beta homologous peptide reduces Alzheimer's disease-associated pathology in transgenic mice. , 2001, The American journal of pathology.

[65]  J. Capitanio,et al.  Contributions of non-human primates to neuroscience research , 2008, The Lancet.

[66]  J. Corr.  Social behavior in aged rhesus macaques. , 2003, Collegium antropologicum.

[67]  Nick C Fox,et al.  Clinical effects of Aβ immunization (AN1792) in patients with AD in an interrupted trial , 2005, Neurology.

[68]  B. Deputte,et al.  Age effect on olfactory discrimination in a non-human primate, Microcebus murinus , 2006, Neurobiology of Aging.

[69]  D. Selkoe,et al.  Alzheimer's disease abeta vaccine reduces central nervous system abeta levels in a non-human primate, the Caribbean vervet. , 2004, The American journal of pathology.

[70]  L. Walker,et al.  Animal models of cerebral beta-amyloid angiopathy. , 1997, Brain research. Brain research reviews.

[71]  J. Kumagai,et al.  Non-human primate model of amyotrophic lateral sclerosis with cytoplasmic mislocalization of TDP-43 , 2012, Brain : a journal of neurology.

[72]  J. Robine,et al.  Excess male mortality and age-specific mortality trajectories under different mortality conditions: A lesson from the heat wave of summer 2003 , 2012, Mechanisms of Ageing and Development.

[73]  E. Someren,et al.  Live to the rhythm, slave to the rhythm. , 2007 .

[74]  Thomas Wichmann,et al.  Effects of Transient Focal Inactivation of the Basal Ganglia in Parkinsonian Primates , 2002, The Journal of Neuroscience.

[75]  J. Gelovani,et al.  Imaging in Research Using Nonhuman Primates , 2012 .

[76]  J. Picq.  Aging and social behaviour in captivity in Microcebus murinus. , 1992, Folia primatologica; international journal of primatology.

[77]  C. Johnson,et al.  Comparative study of blood coagulation in nonhuman primates. , 1971, Journal of applied physiology.

[78]  F. Aujard,et al.  Ocular findings in two colonies of gray mouse lemurs (Microcebus murinus). , 2007, Veterinary ophthalmology.