TY - JOUR
T1 - Does the imbalance in the apolipoprotein E isoforms underlie the pathophysiological process of sporadic Alzheimer's disease?
AU - Lozupone, Madia
AU - Imbimbo, Bruno Pietro
AU - Balducci, Claudia
AU - Lo Vecchio, Filomena
AU - Bisceglia, Paola
AU - Latino, Raffaela Rita
AU - Leone, Maurizio
AU - Dibello, Vittorio
AU - Solfrizzi, Vincenzo
AU - Greco, Antonio
AU - Daniele, Antonio
AU - Watling, Mark
AU - Seripa, Davide
AU - Panza, Francesco
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - Alzheimer's disease pathophysiology
KW - anti-apolipoprotein E drugs
KW - apolipoprotein E
KW - apolipoprotein E isoforms
KW - Alzheimer's disease pathophysiology
KW - anti-apolipoprotein E drugs
KW - apolipoprotein E
KW - apolipoprotein E isoforms
UR - http://hdl.handle.net/10807/216404
U2 - 10.1002/alz.12728
DO - 10.1002/alz.12728
M3 - Article
SN - 1552-5279
SP - 353
EP - 368
JO - ALZHEIMER'S & DEMENTIA
JF - ALZHEIMER'S & DEMENTIA
ER -