Cited 2 time in webofscience Cited 2 time in scopus

Differential spatial expression of peripheral olfactory neuron-derived BACE1 induces olfactory impairment by region-specific accumulation of beta-amyloid oligomer

Title
Differential spatial expression of peripheral olfactory neuron-derived BACE1 induces olfactory impairment by region-specific accumulation of beta-amyloid oligomer
Authors
Yoo, Seung JunLee, Ji HyeKim, So YeonSon, Go WoonKim, Jae YeonCho, BongkiYu, Seong WoonChang, Keun ASuh, Yoo HunMoon, Che Il
DGIST Authors
Cho, Bongki; Yu, Seong WoonMoon, Che Il
Issue Date
2017-08
Citation
Cell Death & Disease, 8(8), e2977
Type
Article
Article Type
Article
Keywords
DISEASE MOUSE MODELMILD COGNITIVE IMPAIRMENTALZHEIMERS-DISEASEA-BETATYROSINE-HYDROXYLASETRANSGENIC MICEBULBRATSYSTEMDOPAMINE
ISSN
2041-4889
Abstract
Olfactory dysfunction is a common symptom associated with neurodegenerative diseases including Alzheimer's disease (AD). Although evidence exists to suggest that peripheral olfactory organs are involved in the olfactory dysfunction that accompanies AD pathology, the underlying mechanisms are not fully understood. As confirmed using behavioral tests, transgenic mice overexpressing a Swedish mutant form of human amyloid precursor proteins exhibited olfactory impairments prior to evidence of cognitive impairment. By measuring the expression of tyrosine hydroxylase, we observed that specific regions of the olfactory bulb (OB) in Tg2576 mice, specifically the ventral portion exhibited significant decreases in the number of dopaminergic neurons in the periglomerular regions from the early stage of AD. To confirm the direct linkage between these olfactory impairments and AD-related pathology, beta-site amyloid precursor protein cleaving enzyme 1 (BACE1)-the initiating enzyme in A beta genesis-and beta-amyloid peptide (A beta), hallmarks of AD were analyzed. We found that an increase in BACE1 expression coincided with an elevation of amyloid-beta (A beta) oligomers in the ventral region of OB. Moreover, olfactory epithelium (OE), in particular the ectoturbinate in which axons of olfactory sensory neurons (OSNs) have direct connections with the dendrites of mitral/tufted cells in the ventral part of OB, exhibited significant decreases in both thickness and cell number even at early stages. This result suggests that A beta oligomer toxicity in the OE may have induced a decline in the number of OSNs and functional impairment of the olfactory system. We first demonstrated that disproportionate levels of regional damage in the peripheral olfactory system may be a specific symptom of AD with A beta oligomer accumulation occurring prior to damage within the CNS. This regional damage in the olfactory system early in the progression of AD may be closely related to AD-related pathological abnormality and olfactory dysfunction found in AD patients.
URI
http://hdl.handle.net/20.500.11750/5649
DOI
10.1038/cddis.2017.349
Publisher
Nature Publishing Group
Related Researcher
  • Author Moon, Cheil Moon Lab
  • Research Interests Brain convergent science based on chemical senses; olfaction; 감각신경계 기반 뇌융합과학; 후각 신경계
Files:
Collection:
Department of Brain and Cognitive SciencesMoon Lab1. Journal Articles
Department of Brain and Cognitive SciencesLaboratory of Neuronal Cell Death1. Journal Articles


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