{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T01:56:55Z","timestamp":1788487015758,"version":"build-2803163510"},"reference-count":214,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2023,8,8]],"date-time":"2023-08-08T00:00:00Z","timestamp":1691452800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health\/National Institute","award":["2R01DA029121-01A1"],"award-info":[{"award-number":["2R01DA029121-01A1"]}]},{"name":"National Institutes of Health\/National Institute","award":["1R01DA049737-01"],"award-info":[{"award-number":["1R01DA049737-01"]}]},{"name":"National Institutes of Health\/National Institute","award":["1R01NS117906-01"],"award-info":[{"award-number":["1R01NS117906-01"]}]},{"name":"National Institute of Neurological Disorders and Stroke","award":["2R01DA029121-01A1"],"award-info":[{"award-number":["2R01DA029121-01A1"]}]},{"name":"National Institute of Neurological Disorders and Stroke","award":["1R01DA049737-01"],"award-info":[{"award-number":["1R01DA049737-01"]}]},{"name":"National Institute of Neurological Disorders and Stroke","award":["1R01NS117906-01"],"award-info":[{"award-number":["1R01NS117906-01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The brain is a highly dynamic organ that requires a constant energy source to function normally. This energy is mostly supplied by glucose, a simple sugar that serves as the brain\u2019s principal fuel source. Glucose transport across the blood\u2013brain barrier (BBB) is primarily controlled via sodium-independent facilitated glucose transport, such as by glucose transporter 1 (GLUT1) and 3 (GLUT3). However, other glucose transporters, including GLUT4 and the sodium-dependent transporters SGLT1 and SGLT6, have been reported in vitro and in vivo. When the BBB endothelial layer is crossed, neurons and astrocytes can absorb the glucose using their GLUT1 and GLUT3 transporters. Glucose then enters the glycolytic pathway and is metabolized into adenosine triphosphate (ATP), which supplies the energy to support cellular functions. The transport and metabolism of glucose in the brain are impacted by several medical conditions, which can cause neurological and neuropsychiatric symptoms. Alzheimer\u2019s disease (AD), Parkinson\u2019s disease (PD), epilepsy, traumatic brain injury (TBI), schizophrenia, etc., are a few of the most prevalent disorders, characterized by a decline in brain metabolism or hypometabolism early in the course of the disease. Indeed, AD is considered a metabolic disorder related to decreased brain glucose metabolism, involving brain insulin resistance and age-dependent mitochondrial dysfunction. Although the conventional view is that reduced cerebral metabolism is an effect of neuronal loss and consequent brain atrophy, a growing body of evidence points to the opposite, where hypometabolism is prodromal or at least precedes the onset of brain atrophy and the manifestation of clinical symptoms. The underlying processes responsible for these glucose transport and metabolic abnormalities are complicated and remain poorly understood. This review article provides a comprehensive overview of the current understanding of hypometabolism in AD and potential therapeutic targets.<\/jats:p>","DOI":"10.3390\/cells12162019","type":"journal-article","created":{"date-parts":[[2023,8,8]],"date-time":"2023-08-08T12:35:42Z","timestamp":1691498142000},"page":"2019","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":69,"title":["Hypometabolism, Alzheimer\u2019s Disease, and Possible Therapeutic Targets: An Overview"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8550-7684","authenticated-orcid":false,"given":"Snehal","family":"Raut","sequence":"first","affiliation":[{"name":"Department of Foundational Medical Studies, Oakland University William Beaumont School of Medicine, Rochester, MI 48309, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aditya","family":"Bhalerao","sequence":"additional","affiliation":[{"name":"Department of Foundational Medical Studies, Oakland University William Beaumont School of Medicine, Rochester, MI 48309, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4293-9756","authenticated-orcid":false,"given":"Michael","family":"Powers","sequence":"additional","affiliation":[{"name":"Department of Biological and Biomedical Sciences, Oakland University, Rochester, MI 48309, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minelly","family":"Gonzalez","sequence":"additional","affiliation":[{"name":"Department of Foundational Medical Studies, Oakland University William Beaumont School of Medicine, Rochester, MI 48309, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Mancuso","sequence":"additional","affiliation":[{"name":"Department of Foundational Medical Studies, Oakland University William Beaumont School of Medicine, Rochester, MI 48309, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2827-7162","authenticated-orcid":false,"given":"Luca","family":"Cucullo","sequence":"additional","affiliation":[{"name":"Department of Foundational Medical Studies, Oakland University William Beaumont School of Medicine, Rochester, MI 48309, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1002\/jimd.12071","article-title":"Synaptic energy metabolism and neuronal excitability, in sickness and health","volume":"42","author":"Oyarzabal","year":"2019","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3417","DOI":"10.1113\/jphysiol.2014.282517","article-title":"Non-signalling energy use in the brain","volume":"593","author":"Engl","year":"2015","journal-title":"J. Physiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/j.tins.2013.07.001","article-title":"Sugar for the brain: The role of glucose in physiological and pathological brain function","volume":"36","author":"Mergenthaler","year":"2013","journal-title":"Trends Neurosci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1152\/physrev.00062.2017","article-title":"Brain glucose metabolism: Integration of energetics with function","volume":"99","author":"Dienel","year":"2019","journal-title":"Physiol. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1007\/s00401-018-1893-0","article-title":"Targeting pericytes for therapeutic approaches to neurological disorders","volume":"136","author":"Cheng","year":"2018","journal-title":"Acta Neuropathol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.neuron.2016.05.016","article-title":"Oligodendroglial NMDA receptors regulate glucose import and axonal energy metabolism","volume":"91","author":"Saab","year":"2016","journal-title":"Neuron"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1002\/glia.23316","article-title":"G lia in brain energy metabolism: A perspective","volume":"66","author":"Barros","year":"2018","journal-title":"Glia"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.autneu.2019.01.005","article-title":"How reliable is cerebral blood flow to map changes in neuronal activity?","volume":"217","author":"Lecrux","year":"2019","journal-title":"Auton. Neurosci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"12629","DOI":"10.3390\/ijms131012629","article-title":"The role of glucose transporters in brain disease: Diabetes and Alzheimer\u2019s disease","volume":"13","author":"Shah","year":"2012","journal-title":"Int. J. Mol. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/nrn.2018.19","article-title":"Lactate in the brain: From metabolic end-product to signalling molecule","volume":"19","author":"Magistretti","year":"2018","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Cunnane, S.C., Courchesne-Loyer, A., Vandenberghe, C., St-Pierre, V., Fortier, M., Hennebelle, M., Croteau, E., Bocti, C., Fulop, T., and Castellano, C.-A. (2016). Can ketones help rescue brain fuel supply in later life? Implications for cognitive health during aging and the treatment of Alzheimer\u2019s disease. Front. Mol. Neurosci., 53.","DOI":"10.3389\/fnmol.2016.00053"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1002\/jnr.10079","article-title":"Glucose and lactate metabolism during brain activation","volume":"66","author":"Dienel","year":"2001","journal-title":"J. Neurosci. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1073\/pnas.89.3.1109","article-title":"Direct measurement of brain glucose concentrations in humans by 13C NMR spectroscopy","volume":"89","author":"Gruetter","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1073\/pnas.1513752113","article-title":"Metabolic connectivity mapping reveals effective connectivity in the resting human brain","volume":"113","author":"Riedl","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"6417","DOI":"10.1073\/pnas.101129298","article-title":"Cerebral energetics and the glycogen shunt: Neurochemical basis of functional imaging","volume":"98","author":"Shulman","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"10771","DOI":"10.1073\/pnas.132272299","article-title":"Total neuroenergetics support localized brain activity: Implications for the interpretation of fMRI","volume":"99","author":"Hyder","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.cmet.2018.11.001","article-title":"Revisiting how the brain senses glucose\u2014And why","volume":"29","author":"Bentsen","year":"2019","journal-title":"Cell Metab."},{"key":"ref_18","first-page":"273","article-title":"Feeding active neurons:(re) emergence of a nursing role for astrocytes","volume":"96","author":"Merle","year":"2002","journal-title":"J. Physiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.neuron.2008.01.003","article-title":"The blood-brain barrier in health and chronic neurodegenerative disorders","volume":"57","author":"Zlokovic","year":"2008","journal-title":"Neuron"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1038\/nrn3114","article-title":"Neurovascular pathways to neurodegeneration in Alzheimer\u2019s disease and other disorders","volume":"12","author":"Zlokovic","year":"2011","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.nbd.2009.07.030","article-title":"Structure and function of the blood\u2013brain barrier","volume":"37","author":"Abbott","year":"2010","journal-title":"Neurobiol. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.1111\/j.1471-4159.1986.tb01755.x","article-title":"Distribution of the glucose transporter in the mammalian brain","volume":"46","author":"Dick","year":"1986","journal-title":"J. Neurochem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1046\/j.1471-4159.1994.62010240.x","article-title":"Developmental expression of GLUT1 and GLUT3 glucose transporters in rat brain","volume":"62","author":"Vannucci","year":"1994","journal-title":"J. Neurochem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"18035","DOI":"10.1016\/S0021-9258(18)38267-X","article-title":"Brain-type glucose transporter (GLUT-1) is selectively localized to the blood-brain barrier. Studies with quantitative western blotting and in situ hybridization","volume":"265","author":"Pardridge","year":"1990","journal-title":"J. Biol. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1096\/fasebj.8.13.7926364","article-title":"Glucose transporter proteins in brain","volume":"8","author":"Maher","year":"1994","journal-title":"FASEB J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1002\/glia.440140107","article-title":"The human blood-brain barrier glucose transporter (GLUT1) is a glucose transporter of gray matter astrocytes","volume":"14","author":"Morgello","year":"1995","journal-title":"Glia"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.jchemneu.2004.05.009","article-title":"Distribution and anatomical localization of the glucose transporter 2 (GLUT2) in the adult rat brain\u2014An immunohistochemical study","volume":"28","author":"Arluison","year":"2004","journal-title":"J. Chem. Neuroanat."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1002\/(SICI)1098-1136(199709)21:1<2::AID-GLIA2>3.0.CO;2-C","article-title":"Glucose transporter proteins in brain: Delivery of glucose to neurons and glia","volume":"21","author":"Vannucci","year":"1997","journal-title":"Glia"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S0006-8993(98)00372-2","article-title":"The 45 kDa form of glucose transporter 1 (GLUT1) is localized in oligodendrocyte and astrocyte but not in microglia in the rat brain","volume":"797","author":"Yu","year":"1998","journal-title":"Brain Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1042\/bj3150827","article-title":"Substrate specificity and kinetic parameters of GLUT3 in rat cerebellar granule neurons","volume":"315","author":"Maher","year":"1996","journal-title":"Biochem. J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1007\/s00424-020-02441-x","article-title":"Glucose transporters in brain in health and disease","volume":"472","author":"Koepsell","year":"2020","journal-title":"Pfl\u00fcgers Arch.-Eur. J. Physiol."},{"key":"ref_32","first-page":"741","article-title":"Central regulation of glucose homeostasis","volume":"7","author":"Tups","year":"2011","journal-title":"Compr. Physiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1016\/j.neuron.2016.12.020","article-title":"GLUT4 mobilization supports energetic demands of active synapses","volume":"93","author":"Ashrafi","year":"2017","journal-title":"Neuron"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1766","DOI":"10.1038\/sj.jcbfm.9600521","article-title":"Supply and demand in cerebral energy metabolism: The role of nutrient transporters","volume":"27","author":"Simpson","year":"2007","journal-title":"J. Cereb. Blood Flow Metab. Off. J. Int. Soc. Cereb. Blood Flow Metab."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/(SICI)1098-1136(199805)23:1<1::AID-GLIA1>3.0.CO;2-B","article-title":"Structural organization of the perivascular astrocyte endfeet and their relationship with the endothelial glucose transporter: A confocal microscopy study","volume":"23","author":"Kacem","year":"1998","journal-title":"Glia"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.1177\/0271678X20985946","article-title":"Understanding the brain uptake and permeability of small molecules through the BBB: A technical overview","volume":"41","author":"Chowdhury","year":"2021","journal-title":"J. Cereb. Blood Flow. Metab."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1111\/j.1471-4159.2009.06333.x","article-title":"Astrocytes are poised for lactate trafficking and release from activated brain and for supply of glucose to neurons","volume":"111","author":"Gandhi","year":"2009","journal-title":"J. Neurochem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"38","DOI":"10.3389\/fncel.2013.00038","article-title":"Multifunctional role of astrocytes as gatekeepers of neuronal energy supply","volume":"7","author":"Stobart","year":"2013","journal-title":"Front. Cell. Neurosci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1002\/glia.23271","article-title":"Bioenergetic regulation of microglia","volume":"66","author":"Ghosh","year":"2018","journal-title":"Glia"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1016\/j.cell.2018.05.003","article-title":"Disease-associated microglia: A universal immune sensor of neurodegeneration","volume":"173","author":"Deczkowska","year":"2018","journal-title":"Cell"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.freeradbiomed.2016.04.200","article-title":"Energy metabolism and inflammation in brain aging and Alzheimer\u2019s disease","volume":"100","author":"Yin","year":"2016","journal-title":"Free Radic. Biol. Med."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Cryer, P.E. (1997). Hypoglycemia: Pathophysiology, Diagnosis, and Treatment, Oxford University Press.","DOI":"10.1093\/oso\/9780195113259.001.0001"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"97","DOI":"10.2337\/diaclin.33.2.97","article-title":"Standards of medical care in diabetes\u20142015 abridged for primary care providers","volume":"33","author":"Association","year":"2015","journal-title":"Clin. Diabetes Publ. Am. Diabetes Assoc."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/1550-2783-1-2-7","article-title":"Metabolic effects of the very-low-carbohydrate diets: Misunderstood \u201cvillains\u201d of human metabolism","volume":"1","author":"Manninen","year":"2004","journal-title":"J. Int. Soc. Sports Nutr."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/cc12514","article-title":"Stress hyperglycemia: An essential survival response!","volume":"17","author":"Marik","year":"2013","journal-title":"Crit. Care"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1001\/jama.1968.03150030031006","article-title":"Irreversible hypoglycemia: A complication of alcohol and insulin","volume":"206","author":"Arky","year":"1968","journal-title":"JAMA"},{"key":"ref_47","first-page":"21","article-title":"Lactate and ketone bodies act as energy substrates as well as signal molecules in the brain","volume":"6","author":"Takahashi","year":"2021","journal-title":"Psychol. Pathophysiol. Outcomes Eat."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1146\/annurev.me.24.020173.001415","article-title":"Metabolism of ketone bodies by the brain","volume":"24","author":"Sokoloff","year":"1973","journal-title":"Annu. Rev. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2296","DOI":"10.1016\/j.neurobiolaging.2015.03.012","article-title":"Caloric restriction increases ketone bodies metabolism and preserves blood flow in aging brain","volume":"36","author":"Lin","year":"2015","journal-title":"Neurobiol. Aging"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1038\/jcbfm.2014.206","article-title":"Lactate transport and signaling in the brain: Potential therapeutic targets and roles in body\u2014Brain interaction","volume":"35","author":"Bergersen","year":"2015","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1007\/978-1-4684-5931-9_5","article-title":"Blood-brain barrier transport of glucose, free fatty acids, and ketone bodies","volume":"291","author":"Pardridge","year":"1991","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1016\/j.mehy.2003.11.028","article-title":"High carbohydrate diets and Alzheimer\u2019s disease","volume":"62","author":"Henderson","year":"2004","journal-title":"Med. Hypotheses"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/1743-7075-2-28","article-title":"A ketogenic diet reduces amyloid beta 40 and 42 in a mouse model of Alzheimer\u2019s disease","volume":"2","author":"Wera","year":"2005","journal-title":"Nutr Metab."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.nut.2010.07.021","article-title":"Brain fuel metabolism, aging, and Alzheimer\u2019s disease","volume":"27","author":"Cunnane","year":"2011","journal-title":"Nutrition"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"R1186","DOI":"10.1152\/ajpregu.00113.2016","article-title":"Fatty acid-induced astrocyte ketone production and the control of food intake","volume":"310","author":"Levin","year":"2016","journal-title":"Am. J. Physiol.-Regul. Integr. Comp. Physiol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Scarf\u00f2, G., Piccarducci, R., Daniele, S., Franzoni, F., and Martini, C. (2022). Exploring the Role of Lipid-Binding Proteins and Oxidative Stress in Neurodegenerative Disorders: A Focus on the Neuroprotective Effects of Nutraceutical Supplementation and Physical Exercise. Antioxidants, 11.","DOI":"10.3390\/antiox11112116"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1038\/nn884","article-title":"Early mitochondrial calcium defects in Huntington\u2019s disease are a direct effect of polyglutamines","volume":"5","author":"Panov","year":"2002","journal-title":"Nat. Neurosci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.neuron.2017.11.028","article-title":"Alzheimer\u2019s disease: From firing instability to homeostasis network collapse","volume":"97","author":"Frere","year":"2018","journal-title":"Neuron"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/S0166-2236(03)00067-5","article-title":"The metallobiology of Alzheimer\u2019s disease","volume":"26","author":"Bush","year":"2003","journal-title":"Trends Neurosci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.jocn.2003.12.007","article-title":"Alzheimer\u2019s disease pathogenesis and therapeutic interventions","volume":"11","author":"Parihar","year":"2004","journal-title":"J. Clin. Neurosci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/S1474-4422(10)70277-5","article-title":"Disrupted energy metabolism and neuronal circuit dysfunction in cognitive impairment and Alzheimer\u2019s disease","volume":"10","author":"Kapogiannis","year":"2011","journal-title":"Lancet Neurol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1126\/science.1072994","article-title":"The amyloid hypothesis of Alzheimer\u2019s disease: Progress and problems on the road to therapeutics","volume":"297","author":"Hardy","year":"2002","journal-title":"Science"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1126\/science.1566067","article-title":"Alzheimer\u2019s disease: The amyloid cascade hypothesis","volume":"256","author":"Hardy","year":"1992","journal-title":"Science"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1196\/annals.1427.007","article-title":"Brain glucose hypometabolism and oxidative stress in preclinical Alzheimer\u2019s disease","volume":"1147","author":"Mosconi","year":"2008","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.nbd.2019.03.008","article-title":"Regional hypometabolism in the 3xTg mouse model of Alzheimer\u2019s disease","volume":"127","author":"Adlimoghaddam","year":"2019","journal-title":"Neurobiol. Dis."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1212\/WNL.50.2.380","article-title":"Frontal lobe hypometabolism and depression in Alzheimer\u2019s disease","volume":"50","author":"Hirono","year":"1998","journal-title":"Neurology"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1002\/jnr.23777","article-title":"Cerebral hypoperfusion and glucose hypometabolism: Key pathophysiological modulators promote neurodegeneration, cognitive impairment, and Alzheimer\u2019s disease","volume":"95","author":"Daulatzai","year":"2017","journal-title":"J. Neurosci. Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1016\/j.biopsych.2011.04.023","article-title":"Regional expansion of hypometabolism in Alzheimer\u2019s disease follows amyloid deposition with temporal delay","volume":"71","author":"Grimmer","year":"2012","journal-title":"Biol. Psychiatry"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1007\/s00259-003-1194-1","article-title":"Cerebral metabolic changes accompanying conversion of mild cognitive impairment into Alzheimer\u2019s disease: A PET follow-up study","volume":"30","author":"Drzezga","year":"2003","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"6037","DOI":"10.1073\/pnas.090106797","article-title":"Cerebral metabolic and cognitive decline in persons at genetic risk for Alzheimer\u2019s disease","volume":"97","author":"Small","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Hampel, H., Hu, Y., Hardy, J., Blennow, K., Chen, C., Perry, G., Kim, S.H., Villemagne, V.L., Aisen, P., and Vendruscolo, M. (2023). The amyloid-\u03b2 pathway in Alzheimer\u2019s disease: A plain language summary. Neurodegener. Dis. Manag.","DOI":"10.2217\/nmt-2022-0037"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"102327","DOI":"10.1016\/j.pneurobio.2022.102327","article-title":"Early alterations in brain glucose metabolism and vascular function in a transgenic rat model of Alzheimer\u2019s disease","volume":"217","author":"Joo","year":"2022","journal-title":"Prog. Neurobiol."},{"key":"ref_73","first-page":"287","article-title":"Environmental Enrichment in Murine Models and Its Translation to Human Factors Improving Conditions in Alzheimer Disease","volume":"10","author":"Colavitta","year":"2023","journal-title":"J. Prev. Alzheimer\u2019s Dis."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1002\/alz.12683","article-title":"The role of mitochondrial dysfunction in Alzheimer\u2019s disease pathogenesis","volume":"19","author":"Ashleigh","year":"2023","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/S0304-3940(99)00847-2","article-title":"Early regional cerebral glucose hypometabolism in transgenic mice overexpressing the V717F \u03b2-amyloid precursor protein","volume":"277","author":"Dodart","year":"1999","journal-title":"Neurosci. Lett."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Chadwick, W., Maudsley, S., Hull, W., Havolli, E., Boshoff, E., Hill, M.D., Goetghebeur, P.J., Harrison, D.C., Nizami, S., and Bedford, D.C. (2023). The oDGal Mouse: A Novel, Physiologically Relevant Rodent Model of Sporadic Alzheimer\u2019s Disease. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24086953"},{"key":"ref_77","unstructured":"L\u00f3pez Oliva, E., Trujillo-Estrada, L.I., Sanchez Mejias, E., Mejias-Ortega, M., Fernandez-Valenzuela, J.J., Gomez-Arboledas, A., Davila, J.C., Vitorica, F.J., and Gutierrez-Perez, A. (April, January 28). Astroglial reactivity in response to b-amyloidosis is associated with mithocondrial pathology in the hippocampus of Alzheimer\u2019s transgenic mice. Proceedings of the International Conference on Alzheimer\u2019s and Parkinson\u2019s Diseases and Related Neurological Disorders, Gothenburg, Sweden."},{"key":"ref_78","first-page":"1778","article-title":"Hypometabolism exceeds atrophy in presymptomatic early-onset familial Alzheimer\u2019s disease","volume":"47","author":"Mosconi","year":"2006","journal-title":"J. Nucl. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1002\/ana.10669","article-title":"Limbic hypometabolism in Alzheimer\u2019s disease and mild cognitive impairment","volume":"54","author":"Nestor","year":"2003","journal-title":"Ann. Neurol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"583931","DOI":"10.1155\/2015\/583931","article-title":"Precuneus and cingulate cortex atrophy and hypometabolism in patients with Alzheimer\u2019s disease and mild cognitive impairment: MRI and 18F-FDG PET quantitative analysis using FreeSurfer","volume":"2015","author":"Bailly","year":"2015","journal-title":"BioMed Res. Int."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/0304-3940(95)11270-7","article-title":"Deficits in cerebral glucose metabolism demonstrated by positron emission tomography in individuals at risk of familial Alzheimer\u2019s disease","volume":"186","author":"Kennedy","year":"1995","journal-title":"Neurosci. Lett."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1212\/WNL.56.9.1133","article-title":"Practice parameter: Early detection of dementia: Mild cognitive impairment (an evidence-based review) [RETIRED]: Report of the Quality Standards Subcommittee of the American Academy of Neurology","volume":"56","author":"Petersen","year":"2001","journal-title":"Neurology"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1093\/brain\/118.1.185","article-title":"Chromosome 14 linked familial Alzheimer\u2019s disease: A clinico-pathological study of a single pedigree","volume":"118","author":"Kennedy","year":"1995","journal-title":"Brain"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1001\/jama.1995.03520360056039","article-title":"Apolipoprotein E type 4 allele and cerebral glucose metabolism in relatives at risk for familial Alzheimer disease","volume":"273","author":"Small","year":"1995","journal-title":"JAMA"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1097\/00001756-200103260-00045","article-title":"Impaired cerebral glucose metabolism and cognitive functioning predict deterioration in mild cognitive impairment","volume":"12","author":"Arnaiz","year":"2001","journal-title":"Neuroreport"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s12987-020-00235-y","article-title":"Presence of a mutation in PSEN1 or PSEN2 gene is associated with an impaired brain endothelial cell phenotype in vitro","volume":"18","author":"Raut","year":"2021","journal-title":"Fluids Barriers CNS"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.neuro.2022.01.007","article-title":"Abeta peptides disrupt the barrier integrity and glucose metabolism of human induced pluripotent stem cell-derived brain microvascular endothelial cells","volume":"89","author":"Raut","year":"2022","journal-title":"Neurotoxicology"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.15252\/embj.201695810","article-title":"Brain metabolism in health, aging, and neurodegeneration","volume":"36","author":"Camandola","year":"2017","journal-title":"EMBO J."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"3384","DOI":"10.2337\/diabetes.51.12.3384","article-title":"The Role of Insulin in Human Brain Glucose Metabolism: An 18Fluoro-Deoxyglucose Positron Emission Tomography Study","volume":"51","author":"Bingham","year":"2002","journal-title":"Diabetes"},{"key":"ref_90","first-page":"161","article-title":"Insulin in the brain: Its pathophysiological implications for States related with central insulin resistance, type 2 diabetes and Alzheimer\u2019s disease","volume":"5","year":"2014","journal-title":"Front. Endocrinol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1038\/s41398-021-01345-3","article-title":"Cross-sectional investigation of insulin resistance in youths with autism spectrum disorder. Any role for reduced brain glucose metabolism?","volume":"11","author":"Manco","year":"2021","journal-title":"Transl. Psychiatry"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.3233\/JAD-161256","article-title":"Effects of Regular and Long-Acting Insulin on Cognition and Alzheimer\u2019s Disease Biomarkers: A Pilot Clinical Trial","volume":"57","author":"Craft","year":"2017","journal-title":"J. Alzheimers Dis."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/s12035-012-8339-9","article-title":"Insulin in the brain: Sources, localization and functions","volume":"47","author":"Ghasemi","year":"2013","journal-title":"Mol. Neurobiol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.tem.2005.01.008","article-title":"The role of insulin receptor signaling in the brain","volume":"16","author":"Plum","year":"2005","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"e12953","DOI":"10.1111\/jne.12953","article-title":"Insulin action on astrocytes: From energy homeostasis to behaviour","volume":"33","author":"Gruber","year":"2021","journal-title":"J. Neuroendocr."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.expneurol.2019.04.012","article-title":"Insulin resistance and hippocampal dysfunction: Disentangling peripheral and brain causes from consequences","volume":"318","author":"Grillo","year":"2019","journal-title":"Exp. Neurol."},{"key":"ref_97","first-page":"e29120","article-title":"Pathophysiological Association Between Diabetes Mellitus and Alzheimer\u2019s Disease","volume":"14","author":"Agrawal","year":"2022","journal-title":"Cureus"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"E156","DOI":"10.1152\/ajpendo.00642.2020","article-title":"Insulin action in the brain regulates both central and peripheral functions","volume":"321","author":"Agrawal","year":"2021","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Costantini, L.C., Barr, L.J., Vogel, J.L., and Henderson, S.T. (2008). Hypometabolism as a therapeutic target in Alzheimer\u2019s disease. BMC Neurosci., 9.","DOI":"10.1186\/1471-2202-9-S2-S16"},{"key":"ref_100","first-page":"546","article-title":"Decreased concentrations of GLUT1 and GLUT3 glucose transporters in the brains of patients with Alzheimer\u2019s disease","volume":"35","author":"Simpson","year":"1994","journal-title":"Ann. Neurol. Off. J. Am. Neurol. Assoc. Child Neurol. Soc."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.febslet.2007.12.035","article-title":"Decreased glucose transporters correlate to abnormal hyperphosphorylation of tau in Alzheimer disease","volume":"582","author":"Liu","year":"2008","journal-title":"FEBS Lett."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.neuron.2014.12.032","article-title":"Blood-brain barrier breakdown in the aging human hippocampus","volume":"85","author":"Montagne","year":"2015","journal-title":"Neuron"},{"key":"ref_103","first-page":"757","article-title":"The glucose transporter of the human brain and blood-brain barrier","volume":"24","author":"Kalaria","year":"1988","journal-title":"Ann. Neurol. Off. J. Am. Neurol. Assoc. Child Neurol. Soc."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1042\/bst0220671","article-title":"Glucose transporters in mammalian brain","volume":"22","author":"Simpson","year":"1994","journal-title":"Biochem. Soc. Trans."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"4430","DOI":"10.1016\/j.febslet.2006.07.012","article-title":"Adult neural stem cells express glucose transporters GLUT1 and GLUT3 and regulate GLUT3 expression","volume":"580","author":"Maurer","year":"2006","journal-title":"FEBS Lett."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1097\/00005072-199501000-00005","article-title":"Functional alterations in Alzheimer\u2019s disease: Decreased glucose transporter 3 immunoreactivity in the perforant pathway terminal zone","volume":"54","author":"Harr","year":"1995","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.jalz.2017.09.011","article-title":"Evidence for brain glucose dysregulation in Alzheimer\u2019s disease","volume":"14","author":"An","year":"2018","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/S0006-8993(96)01122-5","article-title":"Forebrain endothelium expresses GLUT4, the insulin-responsive glucose transporter","volume":"744","author":"McCall","year":"1997","journal-title":"Brain Res."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0006-8993(98)00103-6","article-title":"GLUT4 glucose transporter expression in rodent brain: Effect of diabetes","volume":"797","author":"Vannucci","year":"1998","journal-title":"Brain Res."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"113076","DOI":"10.1016\/j.expneurol.2019.113076","article-title":"GluT4: A central player in hippocampal memory and brain insulin resistance","volume":"323","author":"McNay","year":"2020","journal-title":"Exp. Neurol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1111\/j.1471-4159.2009.06320.x","article-title":"Brain glucose transporters, O-GlcNAcylation and phosphorylation of tau in diabetes and Alzheimer\u2019s disease","volume":"111","author":"Liu","year":"2009","journal-title":"J. Neurochem."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Folch, J., Ettcheto, M., Busquets, O., S\u00e1nchez-L\u00f3pez, E., Castro-Torres, R.D., Verdaguer, E., Manzine, P.R., Poor, S.R., Garc\u00eda, M.L., and Olloquequi, J. (2018). The implication of the brain insulin receptor in late onset Alzheimer\u2019s disease dementia. Pharmaceuticals, 11.","DOI":"10.3390\/ph11010011"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"2608","DOI":"10.1007\/s12035-021-02297-x","article-title":"Impact of genetic risk factors for Alzheimer\u2019s disease on brain glucose metabolism","volume":"58","author":"Cho","year":"2021","journal-title":"Mol. Neurobiol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"6799","DOI":"10.1523\/JNEUROSCI.5463-03.2004","article-title":"\u03b2-amyloid peptide at sublethal concentrations downregulates brain-derived neurotrophic factor functions in cultured cortical neurons","volume":"24","author":"Tong","year":"2004","journal-title":"J. Neurosci."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1080\/15548627.2016.1159375","article-title":"Insulin-degrading enzyme secretion from astrocytes is mediated by an autophagy-based unconventional secretory pathway in Alzheimer disease","volume":"12","author":"Son","year":"2016","journal-title":"Autophagy"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1111\/j.1471-4159.2008.05858.x","article-title":"The up-regulation of BACE1 mediated by hypoxia and ischemic injury: Role of oxidative stress and HIF1\u03b1","volume":"108","author":"Guglielmotto","year":"2009","journal-title":"J. Neurochem."},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Versele, R., Sevin, E., Gosselet, F., Fenart, L., and Candela, P. (2022). TNF-\u03b1 and IL-1\u03b2 modulate blood-brain barrier permeability and decrease amyloid-\u03b2 peptide efflux in a human blood-brain barrier model. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231810235"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1196\/annals.1372.039","article-title":"Inflammatory process in type 2 diabetes: The role of cytokines","volume":"1084","author":"Alexandraki","year":"2006","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1016\/S0891-5849(02)00794-3","article-title":"Lipid peroxidation and protein oxidation in Alzheimer\u2019s disease brain: Potential causes and consequences involving amyloid \u03b2-peptide-associated free radical oxidative stress","volume":"32","author":"Butterfield","year":"2002","journal-title":"Free Radic. Biol. Med."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1007\/s00726-003-0048-2","article-title":"Redox regulation of heat shock protein expression in aging and neurodegenerative disorders associated with oxidative stress: A nutritional approach","volume":"25","author":"Calabrese","year":"2003","journal-title":"Amino Acids"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"9078","DOI":"10.1523\/JNEUROSCI.1071-09.2009","article-title":"\u03b2-amyloid oligomers induce phosphorylation of tau and inactivation of insulin receptor substrate via c-Jun N-terminal kinase signaling: Suppression by omega-3 fatty acids and curcumin","volume":"29","author":"Ma","year":"2009","journal-title":"J. Neurosci."},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Simpson, D.S., and Oliver, P.L. (2020). ROS generation in microglia: Understanding oxidative stress and inflammation in neurodegenerative disease. Antioxidants, 9.","DOI":"10.3390\/antiox9080743"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"4028","DOI":"10.2174\/1381612822666160518142226","article-title":"Therapeutic Approaches Targeting Pathological Tau Aggregates","volume":"22","author":"Gerson","year":"2016","journal-title":"Curr. Pharm. Des."},{"key":"ref_124","first-page":"1000","article-title":"Causal treatment of Alzheimer\u2019s disease: Amyloid antibodies","volume":"63","author":"Pawlowski","year":"2022","journal-title":"Inn. Med."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1517\/13543784.2015.1075002","article-title":"Early investigational drugs targeting tau protein for the treatment of Alzheimer\u2019s disease","volume":"24","author":"Anand","year":"2015","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.tins.2018.06.002","article-title":"In search of an identity for amyloid plaques","volume":"41","author":"Huynh","year":"2018","journal-title":"Trends Neurosci."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"142","DOI":"10.3389\/fneur.2015.00142","article-title":"Autosomal dominant Alzheimer disease: A unique resource to study CSF biomarker changes in preclinical AD","volume":"6","author":"Schindler","year":"2015","journal-title":"Front. Neurol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"173554","DOI":"10.1016\/j.ejphar.2020.173554","article-title":"Alzheimer\u2019s disease: Recent treatment strategies","volume":"887","author":"Vaz","year":"2020","journal-title":"Eur. J. Pharmacol."},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Testai, L., Martelli, A., Flori, L., Cicero, A.F.G., and Colletti, A. (2021). Coenzyme Q(10): Clinical Applications beyond Cardiovascular Diseases. Nutrients, 13.","DOI":"10.3390\/nu13051697"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"858","DOI":"10.2174\/1568026615666150827095252","article-title":"Neuroprotection of Coenzyme Q10 in Neurodegenerative Diseases","volume":"16","author":"Yang","year":"2016","journal-title":"Curr. Top Med. Chem."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1001\/archneur.59.10.1541","article-title":"Effects of coenzyme Q10 in early Parkinson disease: Evidence of slowing of the functional decline","volume":"59","author":"Shults","year":"2002","journal-title":"Arch. Neurol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1001\/archneurol.2012.85","article-title":"Antioxidants for Alzheimer disease: A randomized clinical trial with cerebrospinal fluid biomarker measures","volume":"69","author":"Galasko","year":"2012","journal-title":"Arch. Neurol."},{"key":"ref_133","doi-asserted-by":"crossref","unstructured":"Jim\u00e9nez-Jim\u00e9nez, F.J., Alonso-Navarro, H., Garc\u00eda-Mart\u00edn, E., and Ag\u00fandez, J.A. (2023). Coenzyme Q10 and Dementia: A Systematic Review. Antioxidants, 12.","DOI":"10.3390\/antiox12020533"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.pneurobio.2013.06.004","article-title":"Decoding Alzheimer\u2019s disease from perturbed cerebral glucose metabolism: Implications for diagnostic and therapeutic strategies","volume":"108","author":"Chen","year":"2013","journal-title":"Prog. Neurobiol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1080\/10401230500296428","article-title":"A review of antioxidants and Alzheimer\u2019s disease","volume":"17","author":"Frank","year":"2005","journal-title":"Ann. Clin. Psychiatry"},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Adalier, N., and Parker, H. (2016). Vitamin E, Turmeric and Saffron in Treatment of Alzheimer\u2019s Disease. Antioxidants, 5.","DOI":"10.3390\/antiox5040040"},{"key":"ref_137","doi-asserted-by":"crossref","unstructured":"Lloret, A., Esteve, D., Monllor, P., Cervera-Ferri, A., and Lloret, A. (2019). The Effectiveness of Vitamin E Treatment in Alzheimer\u2019s Disease. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20040879"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1001\/jama.2013.282834","article-title":"Effect of vitamin E and memantine on functional decline in Alzheimer disease: The TEAM-AD VA cooperative randomized trial","volume":"311","author":"Dysken","year":"2014","journal-title":"JAMA"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"2379","DOI":"10.1056\/NEJMoa050151","article-title":"Vitamin E and donepezil for the treatment of mild cognitive impairment","volume":"352","author":"Petersen","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1056\/NEJM199704243361704","article-title":"A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer\u2019s disease","volume":"336","author":"Sano","year":"1997","journal-title":"N. Engl. J. Med."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"2106","DOI":"10.1017\/S0007114516001203","article-title":"Curcumin and cognition: A randomised, placebo-controlled, double-blind study of community-dwelling older adults","volume":"115","author":"Brown","year":"2016","journal-title":"Br. J. Nutr."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1016\/S0197-4580(01)00300-1","article-title":"Phenolic anti-inflammatory antioxidant reversal of A\u03b2-induced cognitive deficits and neuropathology","volume":"22","author":"Frautschy","year":"2001","journal-title":"Neurobiol. Aging"},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"Ege, D. (2021). Action mechanisms of curcumin in Alzheimer\u2019s disease and its brain targeted delivery. Materials, 14.","DOI":"10.3390\/ma14123332"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1017\/S0007114515004687","article-title":"Examining the potential clinical value of curcumin in the prevention and diagnosis of Alzheimer\u2019s disease","volume":"115","author":"Goozee","year":"2016","journal-title":"Br. J. Nutr."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1021\/mp700113r","article-title":"Bioavailability of curcumin: Problems and promises","volume":"4","author":"Anand","year":"2007","journal-title":"Mol. Pharm."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"1955","DOI":"10.1016\/j.ejca.2005.05.009","article-title":"Curcumin: The story so far","volume":"41","author":"Sharma","year":"2005","journal-title":"Eur. J. Cancer"},{"key":"ref_147","doi-asserted-by":"crossref","unstructured":"Kuepeli Akkol, E., Bardakc\u0131, H., Y\u00fccel, \u00c7., \u015eeker Karatoprak, G., Karpuz, B., and Khan, H. (2022). A New Perspective on the Treatment of Alzheimer\u2019s Disease and Sleep Deprivation-Related Consequences: Can Curcumin Help?. Oxidative Med. Cell. Longev., 2022.","DOI":"10.1155\/2022\/6168199"},{"key":"ref_148","first-page":"223","article-title":"Alzheimer\u2019s disease: The pros and cons of pharmaceutical, nutritional, botanical, and stimulatory therapies, with a discussion of treatment strategies from the perspective of patients and practitioners","volume":"15","author":"Wollen","year":"2010","journal-title":"Altern Med. Rev."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"3955","DOI":"10.2174\/09298673113209990210","article-title":"Neuroprotective properties of curcumin in Alzheimer\u2019s disease-merits and limitations","volume":"20","author":"Chin","year":"2013","journal-title":"Curr. Med. Chem."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"1997","DOI":"10.1166\/jbn.2019.2837","article-title":"Nanomedicine for the Treatment of Alzheimer\u2019s Disease","volume":"15","author":"Formicola","year":"2019","journal-title":"J. Biomed. Nanotechnol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"2306","DOI":"10.1016\/j.apsb.2020.11.023","article-title":"Evolution of blood-brain barrier in brain diseases and related systemic nanoscale brain-targeting drug delivery strategies","volume":"11","author":"Han","year":"2021","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.jalz.2018.07.222","article-title":"Vascular dysfunction\u2014The disregarded partner of Alzheimer\u2019s disease","volume":"15","author":"Sweeney","year":"2019","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1038\/nrn.2017.48","article-title":"Cerebral blood flow regulation and neurovascular dysfunction in Alzheimer disease","volume":"18","author":"Kisler","year":"2017","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.neuron.2010.09.043","article-title":"Pericytes control key neurovascular functions and neuronal phenotype in the adult brain and during brain aging","volume":"68","author":"Bell","year":"2010","journal-title":"Neuron"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1111\/bpa.12004","article-title":"Deficiency in Mural Vascular Cells Coincides with Blood\u2013Brain Barrier Disruption in A lzheimer\u2019s Disease","volume":"23","author":"Sengillo","year":"2013","journal-title":"Brain Pathol."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"2932","DOI":"10.1038\/ncomms3932","article-title":"Pericyte loss influences Alzheimer-like neurodegeneration in mice","volume":"4","author":"Sagare","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.brainres.2007.08.063","article-title":"Amyloid beta deposition is related to decreased glucose transporter-1 levels and hippocampal atrophy in brains of aged APP\/PS1 mice","volume":"1181","author":"Hooijmans","year":"2007","journal-title":"Brain Res."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/nrneurol.2017.188","article-title":"Blood\u2013brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders","volume":"14","author":"Sweeney","year":"2018","journal-title":"Nat. Rev. Neurol."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1016\/0028-3932(89)90096-1","article-title":"Glucose enhancement of performance on memory tests in young and aged humans","volume":"27","author":"Hall","year":"1989","journal-title":"Neuropsychologia"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1038\/s41593-020-00778-1","article-title":"Gene-based therapies for neurodegenerative diseases","volume":"24","author":"Sun","year":"2021","journal-title":"Nat. Neurosci."},{"key":"ref_161","first-page":"715","article-title":"Pathophysiology of critical illness hyperglycemia in children","volume":"26","author":"Kendirli","year":"2013","journal-title":"J. Pediatr. Endocrinol. Metab."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"117912","DOI":"10.1016\/j.lfs.2020.117912","article-title":"Identification of novel class I and class IIb histone deacetylase inhibitor for Alzheimer\u2019s disease therapeutics","volume":"256","author":"Gupta","year":"2020","journal-title":"Life Sci."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"112193","DOI":"10.1016\/j.ejmech.2020.112193","article-title":"Synthesis and biological evaluation of acridine-based histone deacetylase inhibitors as multitarget agents against Alzheimer\u2019s disease","volume":"192","author":"Tseng","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1007\/s12035-014-8958-4","article-title":"Brain-derived neurotrophic factor in Alzheimer\u2019s disease: Risk, mechanisms, and therapy","volume":"52","author":"Song","year":"2015","journal-title":"Mol. Neurobiol."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1517\/14728222.8.5.391","article-title":"Brain-derived neurotrophic factor as a drug target for CNS disorders","volume":"8","author":"Pezet","year":"2004","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/WCO.0b013e32835bf200","article-title":"Ischemic preconditioning and clinical scenarios","volume":"26","author":"Narayanan","year":"2013","journal-title":"Curr. Opin. Neurol."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"1490","DOI":"10.1089\/scd.2012.0633","article-title":"Cell and gene therapy in Alzheimer\u2019s disease","volume":"22","author":"Glat","year":"2013","journal-title":"Stem Cells Dev."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.ymgmr.2016.12.008","article-title":"Gene therapy for a mouse model of glucose transporter-1 deficiency syndrome","volume":"10","author":"Nakamura","year":"2017","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1111\/j.1582-4934.2010.01038.x","article-title":"Gene therapy in Alzheimer\u2019s disease\u2013potential for disease modification","volume":"14","author":"Nilsson","year":"2010","journal-title":"J. Cell. Mol. Med."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1007\/s00401-018-1932-x","article-title":"Current state of Alzheimer\u2019s fluid biomarkers","volume":"136","author":"Molinuevo","year":"2018","journal-title":"Acta Neuropathol."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"15056","DOI":"10.1038\/nrdp.2015.56","article-title":"Alzheimer\u2019s disease","volume":"1","author":"Masters","year":"2015","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1515\/revneuro-2017-0063","article-title":"Amyloid toxicity in Alzheimer\u2019s disease","volume":"29","author":"Reiss","year":"2018","journal-title":"Rev. Neurosci."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1038\/nrd3505","article-title":"The amyloid cascade hypothesis for Alzheimer\u2019s disease: An appraisal for the development of therapeutics","volume":"10","author":"Karran","year":"2011","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"7904","DOI":"10.1073\/pnas.1217938110","article-title":"Rapid cell death is preceded by amyloid plaque-mediated oxidative stress","volume":"110","author":"Xie","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_175","doi-asserted-by":"crossref","unstructured":"Chan, K.-H., Lam, K.S.-L., Cheng, O.-Y., Kwan, J.S.-C., Ho, P.W.-L., Cheng, K.K.-Y., Chung, S.K., Ho, J.W.-M., Guo, V.Y., and Xu, A. (2012). Adiponectin is protective against oxidative stress induced cytotoxicity in amyloid-beta neurotoxicity. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0052354"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"e21990","DOI":"10.1002\/syn.21990","article-title":"Alzheimer\u2019s disease and metabolic syndrome: A link from oxidative stress and inflammation to neurodegeneration","volume":"71","author":"Espinosa","year":"2017","journal-title":"Synapse"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"2096","DOI":"10.1007\/s11064-011-0533-z","article-title":"Protective effects of walnut extract against amyloid beta peptide-induced cell death and oxidative stress in PC12 cells","volume":"36","author":"Muthaiyah","year":"2011","journal-title":"Neurochem. Res."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"3639","DOI":"10.1523\/JNEUROSCI.4396-06.2007","article-title":"\u03b2-Site amyloid precursor protein cleaving enzyme 1 levels become elevated in neurons around amyloid plaques: Implications for Alzheimer\u2019s disease pathogenesis","volume":"27","author":"Zhao","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1038\/aps.2017.28","article-title":"Amyloid beta: Structure, biology and structure-based therapeutic development","volume":"38","author":"Chen","year":"2017","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_180","first-page":"229","article-title":"Amyloid \u03b2-peptide interactions with neuronal and glial cell plasma membrane: Binding sites and implications for Alzheimer\u2019s disease","volume":"10","author":"Verdier","year":"2004","journal-title":"J. Pept. Sci. Off. Publ. Eur. Pept. Soc."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"19","DOI":"10.2174\/1389203043486937","article-title":"Binding sites of amyloid \u03b2-peptide in cell plasma membrane and implications for Alzheimer\u2019s disease","volume":"5","author":"Verdier","year":"2004","journal-title":"Curr. Protein Pept. Sci."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"100715","DOI":"10.1016\/j.jbc.2021.100715","article-title":"Regulation of tau internalization, degradation, and seeding by LRP1 reveals multiple pathways for tau catabolism","volume":"296","author":"Cooper","year":"2021","journal-title":"J. Biol. Chem."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.2353\/ajpath.2008.070829","article-title":"Co-localization of amyloid beta and tau pathology in Alzheimer\u2019s disease synaptosomes","volume":"172","author":"Fein","year":"2008","journal-title":"Am. J. Pathol."},{"key":"ref_184","doi-asserted-by":"crossref","unstructured":"Cooper, J.M., Lathuiliere, A., Migliorini, M., Arai, A.L., Wani, M.M., Dujardin, S., Muratoglu, S.C., Hyman, B.T., and Strickland, D.K. (2020). LRP1 and SORL1 regulate tau internalization and degradation and enhance tau seeding. BioRxiv.","DOI":"10.1101\/2020.11.17.386581"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1007\/s12035-014-8742-5","article-title":"The role of SORL1 in Alzheimer\u2019s disease","volume":"51","author":"Yin","year":"2015","journal-title":"Mol. Neurobiol."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1007\/s00406-012-0295-x","article-title":"SORL1 genetic variants and cerebrospinal fluid biomarkers of Alzheimer\u2019s disease","volume":"262","author":"Guo","year":"2012","journal-title":"Eur. Arch. Psychiatry Clin. Neurosci."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"2628","DOI":"10.1161\/01.STR.0000143452.85382.d1","article-title":"RAGE (yin) versus LRP (yang) balance regulates Alzheimer amyloid \u03b2-peptide clearance through transport across the blood\u2013brain barrier","volume":"35","author":"Deane","year":"2004","journal-title":"Stroke"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"11495","DOI":"10.1523\/JNEUROSCI.3697-05.2005","article-title":"IgG-assisted age-dependent clearance of Alzheimer\u2019s amyloid \u03b2 peptide by the blood\u2013brain barrier neonatal Fc receptor","volume":"25","author":"Deane","year":"2005","journal-title":"J. Neurosci."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1038\/srep01302","article-title":"Bapineuzumab captures the N-terminus of the Alzheimer\u2019s disease amyloid-beta peptide in a helical conformation","volume":"3","author":"Miles","year":"2013","journal-title":"Sci. Rep."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"808","DOI":"10.2174\/156720511798192718","article-title":"Anti-\u03b2-amyloid immunotherapy for Alzheimer\u2019s disease: Focus on bapineuzumab","volume":"8","author":"Panza","year":"2011","journal-title":"Curr. Alzheimer Res."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.jalz.2015.06.1893","article-title":"Phase 3 solanezumab trials: Secondary outcomes in mild Alzheimer\u2019s disease patients","volume":"12","author":"Siemers","year":"2016","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.biopsych.2017.08.010","article-title":"Anti-amyloid-\u03b2 monoclonal antibodies for Alzheimer\u2019s disease: Pitfalls and promise","volume":"83","year":"2018","journal-title":"Biol. Psychiatry"},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1007\/s00401-015-1489-x","article-title":"Abeta targets of the biosimilar antibodies of Bapineuzumab, Crenezumab, Solanezumab in comparison to an antibody against N-truncated Abeta in sporadic Alzheimer disease cases and mouse models","volume":"130","author":"Bouter","year":"2015","journal-title":"Acta Neuropathol."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1186\/s13195-018-0424-5","article-title":"Amyloid positron emission tomography and cerebrospinal fluid results from a crenezumab anti-amyloid-beta antibody double-blind, placebo-controlled, randomized phase II study in mild-to-moderate Alzheimer\u2019s disease (BLAZE)","volume":"10","author":"Salloway","year":"2018","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1002\/ana.25513","article-title":"Target engagement in an alzheimer trial: Crenezumab lowers amyloid \u03b2 oligomers in cerebrospinal fluid","volume":"86","author":"Yang","year":"2019","journal-title":"Ann. Neurol."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1517\/14656560903044982","article-title":"Development of semagacestat (LY450139), a functional \u03b3-secretase inhibitor, for the treatment of Alzheimer\u2019s disease","volume":"10","author":"Henley","year":"2009","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_197","first-page":"115","article-title":"Neuropathological and biochemical assessments of an Alzheimer\u2019s disease patient treated with the \u03b3-secretase inhibitor semagacestat","volume":"3","author":"Roher","year":"2014","journal-title":"Am. J. Neurodegener. Dis."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"2021","DOI":"10.1185\/03007995.2014.939167","article-title":"Safety profile of semagacestat, a gamma-secretase inhibitor: IDENTITY trial findings","volume":"30","author":"Henley","year":"2014","journal-title":"Curr. Med. Res. Opin."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1016\/S1474-4422(10)70119-8","article-title":"Alzheimer\u2019s disease: Clinical trials and drug development","volume":"9","author":"Mangialasche","year":"2010","journal-title":"Lancet Neurol."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1007\/s12264-018-0249-z","article-title":"Clinical Research on Alzheimer\u2019s Disease: Progress and Perspectives","volume":"34","author":"Sun","year":"2018","journal-title":"Neurosci. Bull."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.3389\/fneur.2019.01125","article-title":"Frontrunner in Translation: Progressive Supranuclear Palsy","volume":"10","author":"Shoeibi","year":"2019","journal-title":"Front. Neurol."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"75","DOI":"10.3233\/JAD-141959","article-title":"A phase II trial of tideglusib in Alzheimer\u2019s disease","volume":"45","author":"Lovestone","year":"2015","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1016\/j.drudis.2022.01.016","article-title":"Challenges and hopes for Alzheimer\u2019s disease","volume":"27","author":"Tatulian","year":"2022","journal-title":"Drug Discov. Today"},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"113320","DOI":"10.1016\/j.ejmech.2021.113320","article-title":"Alzheimer\u2019s disease and its treatment by different approaches: A review","volume":"216","author":"Srivastava","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3233\/JAD-131295","article-title":"Art therapy for Alzheimer\u2019s disease and other dementias","volume":"39","author":"Chancellor","year":"2014","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/j.jshs.2020.01.004","article-title":"Physical exercise in the prevention and treatment of Alzheimer\u2019s disease","volume":"9","author":"Millan","year":"2020","journal-title":"J. Sport Health Sci."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1249\/JSR.0000000000000332","article-title":"Alzheimer\u2019s Disease and Exercise: A Literature Review","volume":"16","author":"Cass","year":"2017","journal-title":"Curr. Sports Med. Rep."},{"key":"ref_208","doi-asserted-by":"crossref","unstructured":"Rusek, M., Pluta, R., U\u0142amek-Kozio\u0142, M., and Czuczwar, S.J. (2019). Ketogenic Diet in Alzheimer\u2019s Disease. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20163892"},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.2174\/1570159X18666200528142429","article-title":"Recent Advancements in Pathogenesis, Diagnostics and Treatment of Alzheimer\u2019s Disease","volume":"18","author":"Khan","year":"2020","journal-title":"Curr. Neuropharmacol."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1080\/1061186X.2021.1927055","article-title":"New advances in brain-targeting nano-drug delivery systems for Alzheimer\u2019s disease","volume":"30","author":"Ouyang","year":"2022","journal-title":"J. Drug Target"},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.jalz.2010.03.003","article-title":"The Alzheimer\u2019s Disease Neuroimaging Initiative positron emission tomography core","volume":"6","author":"Jagust","year":"2010","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"390","DOI":"10.2967\/jnumed.107.045385","article-title":"Multicenter standardized 18F-FDG PET diagnosis of mild cognitive impairment, Alzheimer\u2019s disease, and other dementias","volume":"49","author":"Mosconi","year":"2008","journal-title":"J. Nucl. Med."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1007\/s40336-013-0026-y","article-title":"Glucose metabolism in normal aging and Alzheimer\u2019s disease: Methodological and physiological considerations for PET studies","volume":"1","author":"Mosconi","year":"2013","journal-title":"Clin. Transl. Imaging"},{"key":"ref_214","doi-asserted-by":"crossref","unstructured":"Alzheimer\u2019s Association (2018). 2018 Alzheimer\u2019s disease facts and figures. Alzheimer\u2019s Dement., 14, 367\u2013429.","DOI":"10.1016\/j.jalz.2018.02.001"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/16\/2019\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:27:41Z","timestamp":1760128061000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/16\/2019"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,8]]},"references-count":214,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2023,8]]}},"alternative-id":["cells12162019"],"URL":"https:\/\/doi.org\/10.3390\/cells12162019","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,8]]}}}