Human apolipoprotein E (apoE) is a 299-amino acid secreted glycoprotein binding cholesterol and phospholipids, and with three common isoforms (APOE epsilon 2, APOE epsilon 3, and APOE epsilon 4). The exact mechanism by which APOE gene variants increase/decrease Alzheimer's disease (AD) risk is not fully understood, but APOE isoforms differently affect brain homeostasis and neuroinflammation, blood-brain barrier (BBB) permeability, glial function, synaptogenesis, oral/gut microbiota, neural networks, amyloid beta (A beta) deposition, and tau-mediated neurodegeneration. In this perspective, we propose a comprehensive interpretation of APOE-mediated effects within AD pathophysiology, describing some specific cellular, biochemical, and epigenetic mechanisms and updating the different APOE-targeting approaches being developed as potential AD therapies. Intracisternal adeno-associated viral-mediated delivery of APOE epsilon 2 is being tested in AD APOE epsilon 4/epsilon 4 carriers, while APOE mimetics are being used in subjects with perioperative neurocognitive disorders. Other approaches including APOE epsilon 4 antisense oligonucleotides, anti-APOE epsilon 4 monoclonal antibodies, APOE epsilon 4 structure correctors, and APOE-A beta interaction inhibitors produced positive results in transgenic AD mouse models.

Lozupone, M., Imbimbo, B. P., Balducci, C., Lo Vecchio, F., Bisceglia, P., Latino, R. R., Leone, M., Dibello, V., Solfrizzi, V., Greco, A., Daniele, A., Watling, M., Seripa, D., Panza, F., Does the imbalance in the apolipoprotein E isoforms underlie the pathophysiological process of sporadic Alzheimer's disease?, <<ALZHEIMER'S & DEMENTIA>>, 2022; (7): N/A-N/A. [doi:10.1002/alz.12728] [https://hdl.handle.net/10807/216404]

Does the imbalance in the apolipoprotein E isoforms underlie the pathophysiological process of sporadic Alzheimer's disease?

Lo Vecchio, Filomena;Daniele, Antonio;
2022

Abstract

Human apolipoprotein E (apoE) is a 299-amino acid secreted glycoprotein binding cholesterol and phospholipids, and with three common isoforms (APOE epsilon 2, APOE epsilon 3, and APOE epsilon 4). The exact mechanism by which APOE gene variants increase/decrease Alzheimer's disease (AD) risk is not fully understood, but APOE isoforms differently affect brain homeostasis and neuroinflammation, blood-brain barrier (BBB) permeability, glial function, synaptogenesis, oral/gut microbiota, neural networks, amyloid beta (A beta) deposition, and tau-mediated neurodegeneration. In this perspective, we propose a comprehensive interpretation of APOE-mediated effects within AD pathophysiology, describing some specific cellular, biochemical, and epigenetic mechanisms and updating the different APOE-targeting approaches being developed as potential AD therapies. Intracisternal adeno-associated viral-mediated delivery of APOE epsilon 2 is being tested in AD APOE epsilon 4/epsilon 4 carriers, while APOE mimetics are being used in subjects with perioperative neurocognitive disorders. Other approaches including APOE epsilon 4 antisense oligonucleotides, anti-APOE epsilon 4 monoclonal antibodies, APOE epsilon 4 structure correctors, and APOE-A beta interaction inhibitors produced positive results in transgenic AD mouse models.
Inglese
Lozupone, M., Imbimbo, B. P., Balducci, C., Lo Vecchio, F., Bisceglia, P., Latino, R. R., Leone, M., Dibello, V., Solfrizzi, V., Greco, A., Daniele, A., Watling, M., Seripa, D., Panza, F., Does the imbalance in the apolipoprotein E isoforms underlie the pathophysiological process of sporadic Alzheimer's disease?, <<ALZHEIMER'S & DEMENTIA>>, 2022; (7): N/A-N/A. [doi:10.1002/alz.12728] [https://hdl.handle.net/10807/216404]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/216404
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