TY - JOUR
T1 - Synthetic amyloid-β oligomers drive early pathological progression of Alzheimer's disease in nonhuman primates
AU - Yue, Feng
AU - Feng, Su
AU - Lu, Chunling
AU - Zhang, Ting
AU - Tao, Guoxian
AU - Liu, Jing
AU - Yue, Chunmei
AU - Jing, Naihe
N1 - Funding Information:
This work was supported in part by the National Key Basic Research and Development Program of China ( 2018YFA0108500 , 2019YFA0801402 , 2018YFA0800100 , 2018YFA0108000 , 2018YFA0107200 , 2017YFA0102700 ), "Strategic Priority Research Program" of the Chinese Academy of Sciences , Grant No. ( XDA16020501 , XDA16020404 ), National Natural Science Foundation of China ( 81671224 , 31472056 , 31630043 ), and the Research Start-up Fund of Hainan University ( RZ2100003016 , RZ2000009939 ).
Publisher Copyright:
© 2021 The Authors
PY - 2021/10/22
Y1 - 2021/10/22
N2 - As an insidious and slowly progressive neurodegenerative disorder, Alzheimer's disease (AD) uniquely develops in humans but fails in other species. Therefore, it has been challenged to rebuild human AD in animals, including in non-human primates. Here, we bilaterally delivered synthetic Aβ oligomers (AβOs) into the cerebral parenchyma of cynomolgus monkeys, which rapidly drove the formation of massive Aβ plaques and concomitant neurofibrillary tangles in the cynomolgus brain. The amyloid and tau pathology as well as their co-occurrence in AβO-monkeys were reminiscent of those in patients with AD. In addition, the activated astrocytes and microglia surrounding Aβ plaques indicated the triggered neuroinflammation. The degenerative neurons and synapses around Aβ plaques also emerged in cynomolgus brain. Together, soluble AβOs caused the cascade of pathologic events associated with AD in monkeys as occurred in patients at the early phase, which could facilitate the development of a promising animal model for human AD in non-human primates.
AB - As an insidious and slowly progressive neurodegenerative disorder, Alzheimer's disease (AD) uniquely develops in humans but fails in other species. Therefore, it has been challenged to rebuild human AD in animals, including in non-human primates. Here, we bilaterally delivered synthetic Aβ oligomers (AβOs) into the cerebral parenchyma of cynomolgus monkeys, which rapidly drove the formation of massive Aβ plaques and concomitant neurofibrillary tangles in the cynomolgus brain. The amyloid and tau pathology as well as their co-occurrence in AβO-monkeys were reminiscent of those in patients with AD. In addition, the activated astrocytes and microglia surrounding Aβ plaques indicated the triggered neuroinflammation. The degenerative neurons and synapses around Aβ plaques also emerged in cynomolgus brain. Together, soluble AβOs caused the cascade of pathologic events associated with AD in monkeys as occurred in patients at the early phase, which could facilitate the development of a promising animal model for human AD in non-human primates.
KW - Model organism
KW - Neuroscience
KW - Synthetic biology
UR - https://www.scopus.com/pages/publications/85122762904
U2 - 10.1016/j.isci.2021.103207
DO - 10.1016/j.isci.2021.103207
M3 - Article
AN - SCOPUS:85122762904
SN - 2589-0042
VL - 24
JO - iScience
JF - iScience
IS - 10
M1 - 103207
ER -