Aged chimpanzees exhibit pathologic hallmarks of Alzheimer's disease

被引:86
作者
Edler, Melissa K. [1 ,2 ]
Sherwood, Chet C. [3 ,4 ]
Meindl, Richard S. [5 ]
Hopkins, William D. [6 ,7 ]
Ely, John J. [8 ]
Erwin, Joseph M. [3 ,4 ]
Mufson, Elliott J. [9 ,10 ]
Hof, Patrick R. [11 ,12 ,13 ]
Raghanti, Mary Ann [1 ,5 ]
机构
[1] Kent State Univ, Sch Biomed Sci, Kent, OH 44242 USA
[2] Northeast Ohio Med Univ, Dept Pharmaceut Sci, 4209 State Route 44,RGE 100, Rootstown, OH 44272 USA
[3] George Washington Univ, Dept Anthropol, Washington, DC USA
[4] George Washington Univ, Ctr Adv Study Human Paleobiol, Washington, DC USA
[5] Kent State Univ, Dept Anthropol, Kent, OH 44242 USA
[6] Yerkes Natl Primate Res Ctr, Div Dev & Cognit Neurosci, Atlanta, GA USA
[7] Georgia State Univ, Neurosci Inst, Atlanta, GA 30303 USA
[8] MAEBIOS, Alamogordo, NM USA
[9] Barrow Neurol Inst, Dept Neurobiol, Phoenix, AZ 85013 USA
[10] Barrow Neurol Inst, Dept Neurol, Phoenix, AZ 85013 USA
[11] Icahn Sch Med Mt Sinai, Fishberg Dept Neurosci, New York, NY 10029 USA
[12] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA
[13] New York Consortium Evolutionary Primatol, New York, NY USA
基金
美国国家科学基金会;
关键词
Alzheimer's disease; Amyloid-beta protein; Chimpanzee; Neurofibrillary tangle; Primate; Tau; CEREBRAL AMYLOID ANGIOPATHY; PAIRED HELICAL FILAMENTS; PREFRONTAL CORTEX AREA-9; NONHUMAN PRIMATE MODELS; PROTEIN-TAU TAU; RHESUS-MONKEYS; COGNITIVE IMPAIRMENT; STEREOLOGIC ANALYSIS; RECOGNITION MEMORY; SENILE PLAQUES;
D O I
10.1016/j.neurobiolaging.2017.07.006
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
Alzheimer's disease (AD) is a uniquely human brain disorder characterized by the accumulation of amyloid-beta protein (Ab) into extracellular plaques, neurofibrillary tangles (NFT) made from intracellular, abnormally phosphorylated tau, and selective neuronal loss. We analyzed a large group of aged chimpanzees (n = 20, age 37-62 years) for evidence of Ab and tau lesions in brain regions affected by AD in humans. A beta was observed in plaques and blood vessels, and tau lesions were found in the form of pretangles, NFT, and tau-immunoreactive neuritic clusters. Ab deposition was higher in vessels than in plaques and correlated with increases in tau lesions, suggesting that amyloid build-up in the brain's microvasculature precedes plaque formation in chimpanzees. Age was correlated to greater volumes of Ab plaques and vessels. Tangle pathology was observed in individuals that exhibited plaques and moderate or severe cerebral amyloid angiopathy, a condition in which amyloid accumulates in the brain's vasculature. Amyloid and tau pathology in aged chimpanzees suggests these AD lesions are not specific to the human brain. (C) 2017 Elsevier Inc. All rights reserved.
引用
收藏
页码:107 / 120
页数:14
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