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

Autor:	Lozupone M; Neurodegenerative Disease Unit, Department of Basic Medicine, Neuroscience, and Sense Organs, University of Bari Aldo Moro, Bari, Italy., Imbimbo BP; Department of Research and Development, Chiesi Farmaceutici, Parma, Italy., Balducci C; Department of Neuroscience, Istituto di Ricerche Farmacologiche 'Mario Negri' IRCCS, Milan, Italy., Lo Vecchio F; Research Laboratory, Complex Structure of Geriatrics, Department of Medical Sciences, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy., Bisceglia P; Research Laboratory, Complex Structure of Geriatrics, Department of Medical Sciences, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy., Latino RR; Complex Structure of Neurology, Department of Medical Sciences, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy., Leone M; Complex Structure of Neurology, Department of Medical Sciences, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy., Dibello V; Department of Orofacial Pain and Dysfunction, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam, the Netherlands., Solfrizzi V; 'Cesare Frugoni' Internal and Geriatric Medicine and Memory Unit, University of Bari 'Aldo Moro, Bari, Italy., Greco A; Research Laboratory, Complex Structure of Geriatrics, Department of Medical Sciences, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy., Daniele A; Department of Neuroscience, Catholic University of Sacred Heart, Rome, Italy.; Neurology Unit, IRCCS Fondazione Policlinico Universitario A. Gemelli, Rome, Italy., Watling M; CNS & Pain Department, TranScrip Ltd, Reading, UK., Seripa D; Hematology and Stem Cell Transplant Unit, 'Vito Fazzi' Hospital, Lecce, Italy., Panza F; Unit of Research Methodology and Data Sciences for Population Health, National Institute of Gastroenterology 'Saverio de Bellis,', Research Hospital, Castellana Grotte, Bari, Italy.
Jazyk:	angličtina
Zdroj:	Alzheimer's & dementia : the journal of the Alzheimer's Association [Alzheimers Dement] 2023 Jan; Vol. 19 (1), pp. 353-368. Date of Electronic Publication: 2022 Jul 28.
DOI:	10.1002/alz.12728
Abstrakt:	Human apolipoprotein E (apoE) is a 299-amino acid secreted glycoprotein binding cholesterol and phospholipids, and with three common isoforms (APOE ε2, APOE ε3, and APOE ε4). 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 (Aβ) 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 ε2 is being tested in AD APOE ε4/ε4 carriers, while APOE mimetics are being used in subjects with perioperative neurocognitive disorders. Other approaches including APOE ε4 antisense oligonucleotides, anti-APOE ε4 monoclonal antibodies, APOE ε4 structure correctors, and APOE-Aβ interaction inhibitors produced positive results in transgenic AD mouse models. (© 2022 the Alzheimer's Association.)
Databáze:	MEDLINE
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