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Alzheimer's disease (AD) related pathological processes and impairment in the peripheral olfactory system

Title
Alzheimer's disease (AD) related pathological processes and impairment in the peripheral olfactory system
Authors
Moon, Cheil
DGIST Authors
Moon, Cheil
Issue Date
2018-04-18
Citation
제32회 한림국제심포지움
Type
Conference
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 hydroxylases, 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, β-site amyloid precursor protein cleaving enzyme 1 (BACE1)—the initiating enzyme in Aβ genesis—and β-amyloid peptide (Aβ), hallmarks of AD were analyzed. We found that an increase in BACE1 expression coincided with an elevation of amyloid-β (Aβ) oligomers in the ventral region of OB. Moreover, olfactory epithelium (OE), in particular the ectoturbinate in which axons of olfactory receptor neurons (ORNs) 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 Aβ oligomer toxicity in the OE may have induced a decline in the number of ORNs and functional impairment of the olfactory system. Collectively, we first demonstrated that disproportionate levels of regional damage in the peripheral olfactory system may be a specific symptom of AD with Aβ oligomer accumulation occurring in the early stage. 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/20.500.11750/15047
Publisher
한국과학기술한림원
Related Researcher
  • Author Moon, Cheil Laboratory of Chemical Senses
  • Research Interests Brain convergent science based on chemical senses; olfaction; 감각신경계 기반 뇌융합과학; 후각 신경계
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Collection:
Department of Brain SciencesLaboratory of Chemical Senses2. Conference Papers


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