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Altered Amyloid-β42 and BACE-1 Proteins in Plasma Astrocyte-Derived Exosomes in Hypertensive Patients With Cerebral
Xiaoxiao Liu1, Yuanyuan Liu1, Ran Yao1
1Department of Neurology, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai, China.
Background:
Cerebral microbleeds (CMBs) have been found to promote Alzheimer's disease (AD) progression. Hypertension (HTN) is one of the major etiological factors for CMBs and an important risk factor for AD. However, the association between HTN-related CMBs and AD pathology remains undetermined. This study aims to identify the relationship between HTN-related CMBs and amyloid-β 42 (Aβ42) and β-site amyloid precursor protein cleaving enzyme 1 (BACE-1) levels in plasma astrocyte-derived exosomes (ADEs).
Methods:
In total, 88 HTN participants including 30 with deep/infratentorial (D/I) CMBs, 30 with mixed CMBs, and 28 without CMBs were analyzed. Susceptibility-weighted imaging was performed to assess the location, presence, and number of CMBs. ELISA kits for BACE-1 and Aβ42 were employed to evaluate the levels of astrocyte-derived exosomal proteins.
Results:
The results indicated that plasma ADE levels of Aβ42 were reduced in the HTN + D/I CMBs and HTN + Mixed CMBs groups relative to the HTN-CMBs group. Furthermore, the plasma ADE levels of Aβ42 were significantly associated with CMBs in patients with HTN. However, no significant differences were found in the plasma ADE levels of BACE-1 among the HTN + D/I CMBs, HTN + Mixed CMBs, and HTN-CMBs groups.
Conclusions:
The study revealed that reduced plasma ADE levels of Aβ42 were significantly associated with CMBs in HTN patients. This finding suggests a potential link between HTN-related CMBs and AD-related amyloid-β pathology, offering novel insights into the mechanisms by which HTN-related CMBs promote AD progression.
Insights
Hypertension-related cerebral microbleeds (CMBs) are linked to reduced plasma astrocyte-derived exosome levels of amyloid-beta 42 (Aβ42). This suggests a connection between hypertension, CMBs, and Alzheimer
Area of Science:
- Neuroscience
- Cardiovascular Research
- Biochemistry
Background:
- Cerebral microbleeds (CMBs) are implicated in Alzheimer's disease (AD) progression.
- Hypertension (HTN) is a key factor in CMBs and an AD risk factor.
- The link between HTN-related CMBs and AD pathology is not fully understood.
Purpose of the Study:
- To investigate the relationship between HTN-related CMBs and levels of amyloid-beta 42 (Aβ42) and BACE-1 in plasma astrocyte-derived exosomes (ADEs).
Main Methods:
- Analysis of 88 hypertensive participants, categorized by CMB presence and location (deep/infratentorial or mixed).
- Assessment of CMBs using susceptibility-weighted imaging.
- Quantification of plasma ADE levels of Aβ42 and BACE-1 via ELISA kits.
Main Results:
- Plasma ADE levels of Aβ42 were lower in hypertensive patients with deep/infratentorial or mixed CMBs compared to those without CMBs.
- Plasma ADE Aβ42 levels showed a significant association with CMBs in hypertensive patients.
- No significant differences in plasma ADE BACE-1 levels were observed across the groups.
Conclusions:
- Reduced plasma ADE Aβ42 levels are significantly associated with CMBs in hypertensive patients.
- This suggests a potential link between HTN-related CMBs and AD-related amyloid-beta pathology.
- Findings offer insights into how HTN-related CMBs may accelerate AD progression.
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