التفاصيل البيبلوغرافية
| العنوان: |
Apolipoprotein E Receptor 2 is associated with Alzheimer’s disease pathogenesis |
| المؤلفون: |
Belaidi, Abdel Ali, Bush, Ashley I, Ayton, Scott |
| المصدر: |
Alzheimer's & Dementia ; volume 19, issue S13 ; ISSN 1552-5260 1552-5279 |
| بيانات النشر: |
Wiley |
| سنة النشر: |
2023 |
| المجموعة: |
Wiley Online Library (Open Access Articles via Crossref) |
| الوصف: |
Background Genetic variations to apolipoprotein E (apoE) underlie the strongest risk for Alzheimer´s disease (AD) after aging but it is not yet known how apoE confers risk for AD. While most research is focusing on dysregulations associated with the presence of the risk allele of apoE, several aspects of apoE biology remain poorly understood. In particular, the physiological relevance of apoE interaction with members of the low‐density lipoprotein (LDL) receptor gene family is not well understood. Method Ferroptosis was induced in the N27 neuronal cell model of ferroptosis using multiple agents (erastin, RSL3, iron, cysteine depletion). Genetic variants of apolipoprotein E receptor 2 (apoER2) were generated via site‐directed mutagenesis and expressed in N27 neurons. The severity of ferroptosis was measured by several toxicity assays (MTT, LDH) and lipid peroxide probe (C 11 BODIPY). The association between apoER2 polymorphism and cognition were investigated in two longitudinal studies: the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and the Australian Imaging Biomarkers and Lifestyle Study of Ageing (AIBL). Result We recently reported that apoE is a potent inhibitor of ferroptosis in neuronal cells in a mechanism that involves a receptor‐mediated activation of the PI3K/AKT signaling pathway. In this study, we identified genetic variants of apoER2 (also known as LRP8, a member of the LDL receptor family) that were associated with slower cognitive decline in clinical cohorts of AD. In preliminary work, we show that one apoER2 variant was associated with an increased protection from ferroptosis in an apoE‐dependent process. Conclusion We present evidence for a biological role of apoER2 and its genetic variation on pathologies associated with Alzheimer’s disease, which may help develop new diagnostic and therapeutic approaches towards the disease. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| DOI: |
10.1002/alz.070715 |
| الاتاحة: |
https://doi.org/10.1002/alz.070715 |
| Rights: |
http://onlinelibrary.wiley.com/termsAndConditions#vor |
| رقم الانضمام: |
edsbas.3F49A6F6 |
| قاعدة البيانات: |
BASE |