title: Injected Amyloid Beta in the Olfactory Bulb Transfers to Other Brain Regions via Neural Connections in Mice.
abstract: Alzheimer's disease (AD) is characterized by progressive neuronal degeneration and pathological accumulation of amyloid plaques in the brain. It has been proposed that the prion-like spreading of amyloid beta (Aβ) protein could contribute to the progression of the disease. Olfactory bulb (OB) is one of the earliest brain regions affected in AD and olfaction is easily impaired prior to cognitive symptoms. However, it remains unclear whether Aβ accumulation in the OB would spread along olfactory projections to other connected brain regions and trigger further neurodegeneration. In the present study, we experimentally injected recombinant human Aβ1-42 (monomers and oligomers, respectively) into the mouse OB and tracked the spreading of Aβ to connected brain regions over 3 days. The results showed that both Aβ monomers and oligomers were rapidly and readily transferred from the injection site to interconnected brain regions in a neural connection manner and triggered neuronal apoptosis in the affected brain regions. Oligomeric Aβ1-42 spread more efficiently and induced more neuronal apoptosis in the affected brain regions compared to monomeric Aβ1-42. Therefore, the study provides evidence that Aβ peptides can transfer via neural connections and the pattern of Aβ peptide spreading provides understanding to manage AD.
authors.affiliation: Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, and Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, The First Affiliated Hospital Sun Yat-Sen University, Guangzhou, 510080, China.
authors.forename: Baixuan
authors.initials: B
authors.lastname: He
authors.affiliation: Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, and Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, The First Affiliated Hospital Sun Yat-Sen University, Guangzhou, 510080, China.
authors.forename: Minying
authors.initials: M
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, 999078, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, 999078, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Shi
authors.affiliation: Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, and Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, The First Affiliated Hospital Sun Yat-Sen University, Guangzhou, 510080, China.
authors.forename: Simei
authors.initials: S
authors.lastname: Long
authors.affiliation: Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, and Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, The First Affiliated Hospital Sun Yat-Sen University, Guangzhou, 510080, China.
authors.forename: Xilin
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, and Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, The First Affiliated Hospital Sun Yat-Sen University, Guangzhou, 510080, China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Pei
authors.affiliation: School of Psychology, Nanjing Normal University, Nanjing, China.
authors.forename: Ti-Fei
authors.initials: TF
authors.lastname: Yuan
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, 999078, China. huanxingsu@umac.mo.
authors.forename: Huanxing
authors.initials: H
authors.lastname: Su
authors.affiliation: Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, and Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, The First Affiliated Hospital Sun Yat-Sen University, Guangzhou, 510080, China. liliyao71@163.com.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Yao
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology*; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009830:Olfactory Bulb / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
chemical_list: D016229:Amyloid beta-Peptides
keywords: Alzheimer’s disease; Apoptosis; Neural connections; Olfactory pathway; Oligomers