Lipids and lipoproteins may play a role in the neuropathology of Alzheimer’s disease
Alzheimer’s disease (AD) and other classes of dementia are important public health problems with overwhelming social, physical, and financial effects for patients, society, and their families and caregivers. The pathophysiology of AD is poorly understood despite the extensive number of clinical and...
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| Format: | Article |
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Frontiers Media S.A.
2023-11-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2023.1275932/full |
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| author | Omer Akyol Sumeyya Akyol Mei-Chuan Chou Shioulan Chen Ching-Kuan Liu Salih Selek Jair C. Soares Chu-Huang Chen |
| author_facet | Omer Akyol Sumeyya Akyol Mei-Chuan Chou Shioulan Chen Ching-Kuan Liu Salih Selek Jair C. Soares Chu-Huang Chen |
| author_sort | Omer Akyol |
| collection | DOAJ |
| description | Alzheimer’s disease (AD) and other classes of dementia are important public health problems with overwhelming social, physical, and financial effects for patients, society, and their families and caregivers. The pathophysiology of AD is poorly understood despite the extensive number of clinical and experimental studies. The brain’s lipid-rich composition is linked to disturbances in lipid homeostasis, often associated with glucose and lipid abnormalities in various neurodegenerative diseases, including AD. Moreover, elevated low-density lipoprotein (LDL) cholesterol levels may be related to a higher probability of AD. Here, we hypothesize that lipids, and electronegative LDL (L5) in particular, may be involved in the pathophysiology of AD. Although changes in cholesterol, triglyceride, LDL, and glucose levels are seen in AD, the cause remains unknown. We believe that L5—the most electronegative subfraction of LDL—may be a crucial factor in understanding the involvement of lipids in AD pathology. LDL and L5 are internalized by cells through different receptors and mechanisms that trigger separate intracellular pathways. One of the receptors involved in L5 internalization, LOX-1, triggers apoptotic pathways. Aging is associated with dysregulation of lipid homeostasis, and it is believed that alterations in lipid metabolism contribute to the pathogenesis of AD. Proposed mechanisms of lipid dysregulation in AD include mitochondrial dysfunction, blood–brain barrier disease, neuronal signaling, inflammation, and oxidative stress, all of which lead ultimately to memory loss through deficiency of synaptic integration. Several lipid species and their receptors have essential functions in AD pathogenesis and may be potential biomarkers. |
| first_indexed | 2024-03-11T10:13:15Z |
| format | Article |
| id | doaj.art-d9bf1c62cb3040faa6aa18053b499ccf |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-03-11T10:13:15Z |
| publishDate | 2023-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-d9bf1c62cb3040faa6aa18053b499ccf2023-11-16T14:08:51ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2023-11-011710.3389/fnins.2023.12759321275932Lipids and lipoproteins may play a role in the neuropathology of Alzheimer’s diseaseOmer Akyol0Sumeyya Akyol1Mei-Chuan Chou2Shioulan Chen3Ching-Kuan Liu4Salih Selek5Jair C. Soares6Chu-Huang Chen7Molecular Cardiology, Vascular and Medicinal Research, The Texas Heart Institute, Houston, TX, United StatesNX Prenatal, Houston, TX, United StatesDepartment of Neurology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, TaiwanGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, TaiwanInstitute of Precision Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung, TaiwanDepartment of Psychiatry and Behavioral Sciences, UTHealth Houston McGovern Medical School, Houston, TX, United StatesDepartment of Psychiatry and Behavioral Sciences, UTHealth Houston McGovern Medical School, Houston, TX, United StatesMolecular Cardiology, Vascular and Medicinal Research, The Texas Heart Institute, Houston, TX, United StatesAlzheimer’s disease (AD) and other classes of dementia are important public health problems with overwhelming social, physical, and financial effects for patients, society, and their families and caregivers. The pathophysiology of AD is poorly understood despite the extensive number of clinical and experimental studies. The brain’s lipid-rich composition is linked to disturbances in lipid homeostasis, often associated with glucose and lipid abnormalities in various neurodegenerative diseases, including AD. Moreover, elevated low-density lipoprotein (LDL) cholesterol levels may be related to a higher probability of AD. Here, we hypothesize that lipids, and electronegative LDL (L5) in particular, may be involved in the pathophysiology of AD. Although changes in cholesterol, triglyceride, LDL, and glucose levels are seen in AD, the cause remains unknown. We believe that L5—the most electronegative subfraction of LDL—may be a crucial factor in understanding the involvement of lipids in AD pathology. LDL and L5 are internalized by cells through different receptors and mechanisms that trigger separate intracellular pathways. One of the receptors involved in L5 internalization, LOX-1, triggers apoptotic pathways. Aging is associated with dysregulation of lipid homeostasis, and it is believed that alterations in lipid metabolism contribute to the pathogenesis of AD. Proposed mechanisms of lipid dysregulation in AD include mitochondrial dysfunction, blood–brain barrier disease, neuronal signaling, inflammation, and oxidative stress, all of which lead ultimately to memory loss through deficiency of synaptic integration. Several lipid species and their receptors have essential functions in AD pathogenesis and may be potential biomarkers.https://www.frontiersin.org/articles/10.3389/fnins.2023.1275932/fullAlzheimer’s diseaselipidscholesterolelectronegative LDLLDLRLOX-1 |
| spellingShingle | Omer Akyol Sumeyya Akyol Mei-Chuan Chou Shioulan Chen Ching-Kuan Liu Salih Selek Jair C. Soares Chu-Huang Chen Lipids and lipoproteins may play a role in the neuropathology of Alzheimer’s disease Frontiers in Neuroscience Alzheimer’s disease lipids cholesterol electronegative LDL LDLR LOX-1 |
| title | Lipids and lipoproteins may play a role in the neuropathology of Alzheimer’s disease |
| title_full | Lipids and lipoproteins may play a role in the neuropathology of Alzheimer’s disease |
| title_fullStr | Lipids and lipoproteins may play a role in the neuropathology of Alzheimer’s disease |
| title_full_unstemmed | Lipids and lipoproteins may play a role in the neuropathology of Alzheimer’s disease |
| title_short | Lipids and lipoproteins may play a role in the neuropathology of Alzheimer’s disease |
| title_sort | lipids and lipoproteins may play a role in the neuropathology of alzheimer s disease |
| topic | Alzheimer’s disease lipids cholesterol electronegative LDL LDLR LOX-1 |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2023.1275932/full |
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