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Distinct amyloid precursor protein processing machineries of the olfactory system
Jae Yeon Kim1, Ameer Rasheed1, Seung-Jun Yoo2
1Department of Brain and Cognitive Sciences, Graduate School, Daegu Gyeungbuk Institute of Science and Technology, Daegu, Republic of Korea.
Biochemical and Biophysical Research Communications
|November 4, 2017
Summary
Alzheimer
Area of Science:
- Neuroscience
- Molecular Biology
- Pathology
Background:
- Alzheimer's disease (AD) is linked to abnormal amyloid precursor protein (APP) processing, producing excess beta-amyloid (Aβ).
- Olfactory dysfunction often precedes other AD symptoms, indicating early vulnerability of the olfactory system.
- The reasons for early olfactory system involvement in AD remain unclear.
Purpose of the Study:
- To investigate APP processing and secretase distribution in the olfactory system.
- To understand why the olfactory system is particularly susceptible to AD pathology.
Main Methods:
- Examined secretase distribution and APP processing levels in the olfactory system.
- Compared healthy and AD-affected olfactory tissues.
- Quantified APP c-terminal fragments (CTF) and Aβ*56 accumulation.
Main Results:
- The olfactory system exhibits unique APP processing machinery with higher γ-secretase expression and activity in the olfactory epithelium (OE) compared to other brain regions.
- Increased presenilin 2 (a γ-secretase component) expression was observed in the OE during AD progression.
- Neurotoxic Aβ*56 accumulated faster in the OE of AD subjects.
Conclusions:
- The olfactory system possesses distinct APP processing mechanisms that differ from other brain areas.
- These unique mechanisms contribute to the early accumulation of toxic Aβ species in the olfactory system during AD.
- Findings provide insights into olfactory deficits associated with Alzheimer's disease.
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