{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T13:04:29Z","timestamp":1791551069329,"version":"4.3.4"},"reference-count":146,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2017,6,27]],"date-time":"2017-06-27T00:00:00Z","timestamp":1498521600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Accumulating evidence in mice models of accelerated senescence indicates a rescuing role of ascorbic acid in premature aging. Supplementation of ascorbic acid appeared to halt cell growth, oxidative stress, telomere attrition, disorganization of chromatin, and excessive secretion of inflammatory factors, and extend lifespan. Interestingly, ascorbic acid (AA) was also found to positively modulate inflamm-aging and immunosenescence, two hallmarks of biological aging. Moreover, ascorbic acid has been shown to epigenetically regulate genome integrity and stability, indicating a key role of targeted nutrition in healthy aging. Growing in vivo evidence supports the role of ascorbic acid in ameliorating factors linked to Alzheimer\u2019s disease (AD) pathogenesis, although evidence in humans yielded equivocal results. The neuroprotective role of ascorbic acid not only relies on the general free radical trapping, but also on the suppression of pro-inflammatory genes, mitigating neuroinflammation, on the chelation of iron, copper, and zinc, and on the suppression of amyloid-beta peptide (A\u03b2) fibrillogenesis. Epidemiological evidence linking diet, one of the most important modifiable lifestyle factors, and risk of Alzheimer's disease is rapidly increasing. Thus, dietary interventions, as a way to epigenetically modulate the human genome, may play a role in the prevention of AD. The present review is aimed at providing an up to date overview of the main biological mechanisms that are associated with ascorbic acid supplementation\/bioavailability in the process of aging and Alzheimer\u2019s disease. In addition, we will address new fields of research and future directions.<\/jats:p>","DOI":"10.3390\/nu9070670","type":"journal-article","created":{"date-parts":[[2017,6,28]],"date-time":"2017-06-28T10:25:56Z","timestamp":1498645556000},"page":"670","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":221,"title":["Vitamin C, Aging and Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"9","author":[{"given":"Fiammetta","family":"Monacelli","sequence":"first","affiliation":[{"name":"Section of Geriatrics, Department of Internal Medicine and Medical Specialties (DIMI), University of Genoa, Genoa 16132, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica","family":"Acquarone","sequence":"additional","affiliation":[{"name":"Section of Geriatrics, Department of Internal Medicine and Medical Specialties (DIMI), University of Genoa, Genoa 16132, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Giannotti","sequence":"additional","affiliation":[{"name":"Section of Geriatrics, Department of Internal Medicine and Medical Specialties (DIMI), University of Genoa, Genoa 16132, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Borghi","sequence":"additional","affiliation":[{"name":"Section of Geriatrics, Department of Internal Medicine and Medical Specialties (DIMI), University of Genoa, Genoa 16132, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessio","family":"Nencioni","sequence":"additional","affiliation":[{"name":"Section of Geriatrics, Department of Internal Medicine and Medical Specialties (DIMI), University of Genoa, Genoa 16132, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1126\/science.1209290","article-title":"7 billion and counting","volume":"333","author":"Bloom","year":"2011","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2313","DOI":"10.1016\/j.jprot.2011.06.005","article-title":"Oxidative stress, inflamm-aging and immunosenescence","volume":"74","author":"Cannizzo","year":"2011","journal-title":"J. Proteom."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.1093\/gerona\/glu057","article-title":"Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases","volume":"69","author":"Franceschi","year":"2014","journal-title":"J. Gerontol. Ser. A Biol. Sci. Med. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.mad.2006.11.015","article-title":"Inflammatory networks in ageing, age-related diseases and longevity","volume":"128","author":"Vasto","year":"2007","journal-title":"Mech. Ageing Dev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1097\/MCO.0b013e32835ada13","article-title":"Inflamm-ageing","volume":"16","author":"Cevenini","year":"2013","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1016\/j.jamda.2013.05.009","article-title":"Proinflammatory cytokines, aging, and age-related diseases","volume":"14","author":"Michaud","year":"2013","journal-title":"J. Am. Med. Dir. Assoc."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1111\/j.1749-6632.2000.tb06651.x","article-title":"Inflamm-aging. An evolutionary perspective on immunosenescence","volume":"908","author":"Franceschi","year":"2000","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/s13148-015-0068-2","article-title":"From inflammaging to healthy aging by dietary lifestyle choices: Is epigenetics the key to personalized nutrition?","volume":"7","author":"Declerck","year":"2015","journal-title":"Clin. Epigenetics"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.mad.2013.12.001","article-title":"Combating inflammaging through a Mediterranean whole diet approach: The nu-age project\u2019s conceptual framework and design","volume":"136","author":"Santoro","year":"2014","journal-title":"Mech. Ageing Dev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.mad.2014.03.001","article-title":"Reprint of: A parallel randomized trial on the effect of a healthful diet on inflammageing and its consequences in European elderly people: Design of the nu-age dietary intervention study","volume":"136","author":"Berendsen","year":"2014","journal-title":"Mech. Ageing Dev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1016\/j.numecd.2015.09.002","article-title":"Prospective association between the dietary inflammatory index and metabolic syndrome: Findings from the su.Vi.Max study","volume":"25","author":"Neufcourt","year":"2015","journal-title":"Nutr. Metab. Cardiovasc. Dis. NMCD"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1080\/07315724.2003.10719272","article-title":"Vitamin C as an antioxidant: Evaluation of its role in disease prevention","volume":"22","author":"Padayatty","year":"2003","journal-title":"J. Am. Coll. Nutr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/1475-2891-2-7","article-title":"Vitamin C in human health and disease is still a mystery? An overview","volume":"2","author":"Naidu","year":"2003","journal-title":"Nutr. J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/S0003-9861(02)00678-1","article-title":"Age-related decline of sodium-dependent ascorbic acid transport in isolated rat hepatocytes","volume":"410","author":"Michels","year":"2003","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.2741\/4160","article-title":"Effects of vitamin c on health: A review of evidence","volume":"18","author":"Grosso","year":"2013","journal-title":"Front. Biosci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1080\/10715760500104025","article-title":"Review: When is an antioxidant not an antioxidant? A review of novel actions and reactions of vitamin C","volume":"39","author":"Duarte","year":"2005","journal-title":"Free Radic. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s00228-005-0009-7","article-title":"Antioxidants and endothelial nitric oxide synthesis","volume":"62","author":"Regine","year":"2006","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1074\/jbc.M004392200","article-title":"l-ascorbic acid potentiates endothelial nitric oxide synthesis via a chemical stabilization of tetrahydrobiopterin","volume":"276","author":"Heller","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2082","DOI":"10.1016\/j.freeradbiomed.2012.03.022","article-title":"Ascorbate stimulates endothelial nitric oxide synthase enzyme activity by rapid modulation of its phosphorylation status","volume":"52","author":"Ladurner","year":"2012","journal-title":"Free Radic. Biol. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0027-5107(01)00072-0","article-title":"Vitamin C and genomic stability","volume":"475","author":"Halliwell","year":"2001","journal-title":"Mutat. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.1007\/s00018-016-2145-x","article-title":"The epigenetic role of vitamin C in health and disease","volume":"73","author":"Camarena","year":"2016","journal-title":"Cell. Mol. Life Sci. CMLS"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1146\/annurev-nutr-071714-034228","article-title":"Regulation of the epigenome by vitamin C","volume":"35","author":"Young","year":"2015","journal-title":"Annu. Rev. Nutr."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"10396","DOI":"10.1021\/ja4028346","article-title":"Ascorbic acid enhances Tet-mediated 5-methylcytosine oxidation and promotes DNA demethylation in mammals","volume":"135","author":"Yin","year":"2013","journal-title":"J. Am. Chem. Soc."},{"key":"ref_24","first-page":"292","article-title":"Vitamin c transporter gene polymorphisms, dietary vitamin C and serum ascorbic acid","volume":"2","author":"Cahill","year":"2009","journal-title":"J. Nutr. Nutr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1093\/clinchem\/46.10.1619","article-title":"The haptoglobin 2-2 phenotype affects serum markers of iron status in healthy males","volume":"46","author":"Langlois","year":"2000","journal-title":"Clin. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1007\/s00394-010-0147-2","article-title":"Vitamin C levels in blood are influenced by polymorphisms in glutathione S-transferases","volume":"50","author":"Horska","year":"2011","journal-title":"Eur. J. Nutr."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"529","DOI":"10.3109\/09637486.2014.898258","article-title":"New criteria for supplementation of selected micronutrients in the era of nutrigenetics and nutrigenomics","volume":"65","author":"Schwartz","year":"2014","journal-title":"Int. J. Food Sci. Nutr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1038\/nature12362","article-title":"Vitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells","volume":"500","author":"Blaschke","year":"2013","journal-title":"Nature"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2917","DOI":"10.1001\/jama.1983.03330450047024","article-title":"Association between nutritional status and cognitive functioning in a healthy elderly population","volume":"249","author":"Goodwin","year":"1983","journal-title":"JAMA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1111\/j.1749-6632.2010.05189.x","article-title":"Ascorbate improves metabolic abnormalities in Wrn mutant mice but not the free radical scavenger catechin","volume":"1197","author":"Lebel","year":"2010","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"458","DOI":"10.18632\/aging.100902","article-title":"Vitamin C modulates the metabolic and cytokine profiles, alleviates hepatic endoplasmic reticulum stress, and increases the life span of gulo\u2212\/\u2212 mice","volume":"8","author":"Aumailley","year":"2016","journal-title":"Aging"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Dallaire, A., Proulx, S., Simard, M.J., and Lebel, M. (2014). Expression profile of Caenorhabditis elegans mutant for the Werner syndrome gene ortholog reveals the impact of vitamin C on development to increase life span. BMC Genom., 15.","DOI":"10.1186\/1471-2164-15-940"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1007\/s13238-016-0278-1","article-title":"Vitamin C alleviates aging defects in a stem cell model for Werner syndrome","volume":"7","author":"Li","year":"2016","journal-title":"Protein Cell"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1096\/fj.09-137133","article-title":"Vitamin C restores healthy aging in a mouse model for Werner syndrome","volume":"24","author":"Massip","year":"2010","journal-title":"FASEB J."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Pangrazzi, L., Meryk, A., Naismith, E., Koziel, R., Lair, J., Krismer, M., Trieb, K., and Grubeck-Loebenstein, B. (2016). \u201cInflamm-aging\u201d influences immune cell survival factors in human bone marrow. Eur. J. Immunol., 47.","DOI":"10.1002\/eji.201646570"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"29","DOI":"10.3389\/fcell.2014.00029","article-title":"Ascorbic acid is a dose-dependent inhibitor of adipocyte differentiation, probably by reducing camp pool","volume":"2","author":"Rahman","year":"2014","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Rahman, F., Bordignon, B., Culerrier, R., Peiretti, F., Spicuglia, S., Djabali, M., Landrier, J.F., and Fontes, M. (2016). Ascorbic acid drives the differentiation of mesoderm-derived embryonic stem cells. Involvement of p38 MAPK\/CREB and SVCT2 transporter. Mol. Nutr. Food Res., 61.","DOI":"10.1002\/mnfr.201600506"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/j.bbrc.2015.03.136","article-title":"Endogenous ROS levels are increased in replicative senescence in human bone marrow mesenchymal stromal cells","volume":"460","author":"Jeong","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.exger.2015.10.012","article-title":"Impact of vitamin C on the cardiometabolic and inflammatory profiles of mice lacking a functional Werner syndrome protein helicase","volume":"72","author":"Aumailley","year":"2015","journal-title":"Exp. Gerontol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1017\/S0007114514003857","article-title":"High dietary intake of vitamin c suppresses age-related thymic atrophy and contributes to the maintenance of immune cells in vitamin C-deficient senescence marker protein-30 knockout mice","volume":"113","author":"Uchio","year":"2015","journal-title":"Br. J. Nutr."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1111\/ggi.12162","article-title":"Ascorbic acid prevents protein oxidation in livers of senescence marker protein-30\/gluconolactonase knockout mice","volume":"14","author":"Sato","year":"2014","journal-title":"Geriatr. Gerontol. Int."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3604","DOI":"10.1039\/C5FO00738K","article-title":"Consumption of high-dose vitamin C (1250 mg per day) enhances functional and structural properties of serum lipoprotein to improve anti-oxidant, anti-atherosclerotic, and anti-aging effects via regulation of anti-inflammatory microrna","volume":"6","author":"Kim","year":"2015","journal-title":"Food Funct."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/j.freeradbiomed.2008.12.018","article-title":"Vitamin c function in the brain: Vital role of the ascorbate transporter SVCT2","volume":"46","author":"Harrison","year":"2009","journal-title":"Free Radic. Biol. Med."},{"key":"ref_44","first-page":"1689","article-title":"Vitamin c promotes in vitro proliferation of bone marrow mesenchymal stem cells derived from aging mice","volume":"35","author":"Zheng","year":"2015","journal-title":"J. Sourn Med. Univ."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"561","DOI":"10.2174\/138945012799499749","article-title":"Molecular targeting regulation of proliferation and differentiation of the bone marrow-derived mesenchymal stem cells or mesenchymal stromal cells","volume":"13","author":"Chen","year":"2012","journal-title":"Curr. Drug Targets"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Yang, W., and Hekimi, S. (2010). A mitochondrial superoxide signal triggers increased longevity in Caenorhabditis elegans. PLoS Biol., 8.","DOI":"10.1371\/journal.pbio.1000556"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"5785","DOI":"10.1073\/pnas.1116158109","article-title":"Superoxide dismutase is dispensable for normal animal lifespan","volume":"109","author":"Hekimi","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1111\/acel.12528","article-title":"Antioxidants reveal an inverted U-shaped dose-response relationship between reactive oxygen species levels and the rate of aging in Caenorhabditis elegans","volume":"16","author":"Desjardins","year":"2017","journal-title":"Aging Cell"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.3945\/jn.116.235119","article-title":"Nutrigenomics at the interface of aging, lifespan, and cancer prevention","volume":"146","author":"Riscuta","year":"2016","journal-title":"J. Nutr."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.maturitas.2017.01.006","article-title":"Oxidative stress and frailty: A systematic review and synthesis of the best evidence","volume":"99","author":"Soysal","year":"2017","journal-title":"Maturitas"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.archger.2015.12.001","article-title":"Consumption of star fruit juice on pro-inflammatory markers and walking distance in the community dwelling elderly","volume":"64","author":"Leelarungrayub","year":"2016","journal-title":"Arch. Gerontol. Geriatr."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.2147\/CIA.S110718","article-title":"A preliminary study on the effects of star fruit consumption on antioxidant and lipid status in elderly Thai individuals","volume":"11","author":"Leelarungrayub","year":"2016","journal-title":"Clin. Interv. Aging"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"209","DOI":"10.4172\/2157-7633.1000209","article-title":"Vitamin C transporters, recycling and the bystander effect in the nervous system: SVCT2 versus gluts","volume":"4","author":"Nualart","year":"2014","journal-title":"J. Stem Cell Res. Ther."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/S0166-2236(99)01543-X","article-title":"Ascorbate regulation and its neuroprotective role in the brain","volume":"23","author":"Rice","year":"2000","journal-title":"Trends Neurosci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1002\/jnr.10647","article-title":"Ascorbate-induced differentiation of embryonic cortical precursors into neurons and astrocytes","volume":"73","author":"Lee","year":"2003","journal-title":"J. Neurosci. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1002\/jnr.21204","article-title":"Ascorbate transport by primary cultured neurons and its role in neuronal function and protection against excitotoxicity","volume":"85","author":"Qiu","year":"2007","journal-title":"J. Neurosci. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1752","DOI":"10.3390\/nu6041752","article-title":"Ascorbic acid and the brain: Rationale for the use against cognitive decline","volume":"6","author":"Harrison","year":"2014","journal-title":"Nutrients"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"28194","DOI":"10.3390\/ijms161226095","article-title":"Old things new view: Ascorbic acid protects the brain in neurodegenerative disorders","volume":"16","author":"Acuna","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"472932","DOI":"10.1155\/2012\/472932","article-title":"Antioxidant therapies for Alzheimer\u2019s disease","volume":"2012","author":"Feng","year":"2012","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"303","DOI":"10.3233\/JAD-130002","article-title":"Survival rate in patients affected by dementia followed by memory clinics (UVA) in Italy","volume":"36","author":"Ientile","year":"2013","journal-title":"J. Alzheimers Dis."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/1742-2094-1-21","article-title":"Brain inflammation and oxidative stress in a transgenic mouse model of Alzheimer-like brain amyloidosis","volume":"1","author":"Yao","year":"2004","journal-title":"J. Neuroinflamm."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1016\/j.neurobiolaging.2010.07.008","article-title":"Pro-oxidant diet enhances beta\/gamma secretase-mediated APP processing in APP\/PS1 transgenic mice","volume":"33","author":"Choudhry","year":"2012","journal-title":"Neurobiol. Aging"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1007\/s00401-013-1177-7","article-title":"The amyloid cascade-inflammatory hypothesis of Alzheimer disease: Implications for therapy","volume":"126","author":"McGeer","year":"2013","journal-title":"Acta Neuropathol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.ijdevneu.2004.07.006","article-title":"Aging-related increase in oxidative stress correlates with developmental pattern of beta-secretase activity and beta-amyloid plaque formation in transgenic Tg2576 mice with Alzheimer-like pathology","volume":"22","author":"Apelt","year":"2004","journal-title":"Int. J. Dev. Neurosci. Off. J. Int. Soc. Dev. Neurosci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1159\/000334901","article-title":"The antioxidant N-acetylcysteine prevents the mitochondrial fragmentation induced by soluble amyloid-beta peptide oligomers","volume":"10","author":"Sanmartin","year":"2012","journal-title":"Neuro-Degener. Dis."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"5589","DOI":"10.1523\/JNEUROSCI.6566-10.2011","article-title":"Amyloid beta-induced impairments in hippocampal synaptic plasticity are rescued by decreasing mitochondrial superoxide","volume":"31","author":"Ma","year":"2011","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1001\/jamaneurol.2013.5847","article-title":"Amyloid-beta and tau: The trigger and bullet in Alzheimer disease pathogenesis","volume":"71","author":"Bloom","year":"2014","journal-title":"JAMA Neurol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1089\/ars.2007.1703","article-title":"Alzheimer\u2019s disease: A lesson from mitochondrial dysfunction","volume":"9","author":"Moreira","year":"2007","journal-title":"Antioxid. Redox Signal."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"255","DOI":"10.4161\/cib.19548","article-title":"Cytoplasmic superoxide radical: A possible contributing factor to intracellular abeta oligomerization in Alzheimer disease","volume":"5","author":"Murakami","year":"2012","journal-title":"Commun. Integr. Biol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"11193","DOI":"10.1073\/pnas.2135061100","article-title":"Copper, beta-amyloid, and Alzheimer\u2019s disease: Tapping a sensitive connection","volume":"100","author":"Bush","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1007\/s00249-007-0228-1","article-title":"Twenty years of metallo-neurobiology: Where to now?","volume":"37","author":"Bush","year":"2008","journal-title":"Eur. Biophys. J. EBJ"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/s11010-010-0563-x","article-title":"Metals, oxidative stress and neurodegenerative disorders","volume":"345","author":"Jomova","year":"2010","journal-title":"Mol. Cell. Biochem."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1515\/cclm-2012-0829","article-title":"Pentosidine determination in CSF: A potential biomarker of Alzheimer\u2019s disease?","volume":"52","author":"Monacelli","year":"2014","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1016\/j.freeradbiomed.2007.05.037","article-title":"Roles of amyloid beta-peptide-associated oxidative stress and brain protein modifications in the pathogenesis of Alzheimer\u2019s disease and mild cognitive impairment","volume":"43","author":"Butterfield","year":"2007","journal-title":"Free Radic. Biol. Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"517","DOI":"10.3233\/JAD-2002-4608","article-title":"Plasma susceptibility to free radical-induced antioxidant consumption and lipid peroxidation is increased in very old subjects with Alzheimer disease","volume":"4","author":"Polidori","year":"2002","journal-title":"J. Alzheimers Dis."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1002\/ana.410370609","article-title":"Expression of heme oxygenase-1 in the senescent and Alzheimer-diseased brain","volume":"37","author":"Schipper","year":"1995","journal-title":"Ann. Neurol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1006\/abbi.1998.0755","article-title":"Biological tyrosine nitration: A pathophysiological function of nitric oxide and reactive oxygen species","volume":"356","author":"Ischiropoulos","year":"1998","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"5847","DOI":"10.1007\/s12035-015-9497-3","article-title":"Dehydroascorbic acid promotes cell death in neurons under oxidative stress: A protective role for astrocytes","volume":"53","author":"Ferrada","year":"2016","journal-title":"Mol. Neurobiol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/978-94-007-2199-9_6","article-title":"Vitamin c transport and its role in the central nervous system","volume":"56","author":"May","year":"2012","journal-title":"Sub-Cell. Biochem."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"77","DOI":"10.3233\/JAD-2011-101425","article-title":"Increased protein and lipid oxidative damage in mitochondria isolated from lymphocytes from patients with Alzheimer\u2019s disease: Insights into the role of oxidative stress in Alzheimer\u2019s disease and initial investigations into a potential biomarker for this dementing disorder","volume":"24","author":"Sultana","year":"2011","journal-title":"J. Alzheimers Dis."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1021\/cn500308h","article-title":"Vitamin C deficiency in the brain impairs cognition, increases amyloid accumulation and deposition, and oxidative stress in APP\/PSEN1 and normally aging mice","volume":"6","author":"Dixit","year":"2015","journal-title":"ACS Chem. Neurosci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"9998","DOI":"10.1074\/jbc.M113.511345","article-title":"Capturing a reactive state of amyloid aggregates: Nmr-based characterization of copper-bound Alzheimer disease amyloid beta-fibrils in a redox cycle","volume":"289","author":"Parthasarathy","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"15656","DOI":"10.1074\/jbc.272.25.15656","article-title":"Antioxidant activity of vitamin C in iron-overloaded human plasma","volume":"272","author":"Berger","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1007\/s12031-016-0817-5","article-title":"Dual role of vitamin C on the neuroinflammation mediated neurodegeneration and memory impairments in colchicine induced rat model of Alzheimer disease","volume":"60","author":"Sil","year":"2016","journal-title":"J. Mol. Neurosci. MN"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.pbb.2009.06.006","article-title":"Vitamin C reduces spatial learning deficits in middle-aged and very old APP\/PSEN1 transgenic and wild-type mice","volume":"93","author":"Harrison","year":"2009","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.brainres.2006.04.047","article-title":"Ascorbic acid protects SH-SY5Y neuroblastoma cells from apoptosis and death induced by beta-amyloid","volume":"1097","author":"Huang","year":"2006","journal-title":"Brain Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"360","DOI":"10.2174\/1871527315666151110130139","article-title":"Neuroprotection by vitamin c against ethanol-induced neuroinflammation associated neurodegeneration in the developing rat brain","volume":"15","author":"Ahmad","year":"2016","journal-title":"CNS Neurol. Disord. Drug Targets"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1002\/jnr.23276","article-title":"Ascorbate prevents cell death from prolonged exposure to glutamate in an in vitro model of human dopaminergic neurons","volume":"91","author":"Ballaz","year":"2013","journal-title":"J. Neurosci. Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.foodchem.2015.11.118","article-title":"Metal chelation, radical scavenging and inhibition of abeta(4)(2) fibrillation by food constituents in relation to Alzheimer\u2019s disease","volume":"199","author":"Chan","year":"2016","journal-title":"Food Chem."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"521","DOI":"10.3233\/JAD-2012-120871","article-title":"A review of the major vascular risk factors related to Alzheimer\u2019s disease","volume":"32","author":"Polidori","year":"2012","journal-title":"J. Alzheimers Dis."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3233\/JAD-2011-101971","article-title":"Vitamin c restores behavioral deficits and amyloid-beta oligomerization without affecting plaque formation in a mouse model of Alzheimer\u2019s disease","volume":"26","author":"Murakami","year":"2011","journal-title":"J. Alzheimers Dis."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S0304-3940(02)00087-3","article-title":"Beta-amyloid deposition in the brains of rats chronically infused with thiorphan or lipopolysaccharide: The role of ascorbic acid in the vehicle","volume":"322","author":"Wenk","year":"2002","journal-title":"Neurosci. Lett."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"16","DOI":"10.2174\/187152709787601867","article-title":"Clearance of amyloid-beta peptide across the blood-brain barrier: Implication for therapies in Alzheimer\u2019s disease","volume":"8","author":"Deane","year":"2009","journal-title":"CNS Neurol. Disord. Drug Targets"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1613","DOI":"10.1111\/j.1532-5415.2007.01378.x","article-title":"Assessment of endothelial function in Alzheimer\u2019s disease: Is Alzheimer\u2019s disease a vascular disease?","volume":"55","author":"Dede","year":"2007","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Lam, V., Hackett, M., and Takechi, R. (2016). Antioxidants and dementia risk: Consideration through a cerebrovascular perspective. Nutrients, 8.","DOI":"10.3390\/nu8120828"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.2174\/1567205013666160625082839","article-title":"Nanocapsulated ascorbic acid in combating cerebral ischemia reperfusion-induced oxidative injury in rat brain","volume":"13","author":"Sarkar","year":"2016","journal-title":"Curr. Alzheimer Res."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2523","DOI":"10.1046\/j.1471-4159.1999.0722523.x","article-title":"The glutathione system of peroxide detoxification is less efficient in neurons than in astroglial cells","volume":"72","author":"Dringen","year":"1999","journal-title":"J. Neurochem."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1007\/s12640-009-9108-z","article-title":"Mechanisms involved in the modulation of astroglial resistance to oxidative stress induced by activated microglia: Antioxidative systems, peroxide elimination, radical generation, lipid peroxidation","volume":"17","author":"Rohl","year":"2010","journal-title":"Neurotox. Res."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1177\/1533317512473193","article-title":"The possible role of antioxidant vitamin C in Alzheimer\u2019s disease treatment and prevention","volume":"28","author":"Heo","year":"2013","journal-title":"Am. J. Alzheimers Dis. Other Dement."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1034\/j.1600-079X.2003.00057.x","article-title":"Orally administered melatonin reduces oxidative stress and proinflammatory cytokines induced by amyloid-beta peptide in rat brain: A comparative, in vivo study versus vitamin C and E","volume":"35","author":"Tan","year":"2003","journal-title":"J. Pineal Res."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1089\/jmf.2006.9.281","article-title":"Comparative brain cholinesterase-inhibiting activity of Glycyrrhiza glabra, Myristica fragrans, ascorbic acid, and metrifonate in mice","volume":"9","author":"Dhingra","year":"2006","journal-title":"J. Med. Food"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1016\/0024-3205(79)90341-2","article-title":"Effect of ascorbic acid on release of acetylcholine from synaptic vesicles prepared from different species of animals and release of noradrenaline from synaptic vesicles of rat brain","volume":"24","author":"Kuo","year":"1979","journal-title":"Life Sci."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"27559","DOI":"10.1074\/jbc.M111.243345","article-title":"Suppression of amyloid beta a11 antibody immunoreactivity by vitamin C: Possible role of heparan sulfate oligosaccharides derived from glypican-1 by ascorbate-induced, nitric oxide (no)-catalyzed degradation","volume":"286","author":"Cheng","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"4896","DOI":"10.1021\/jp9095375","article-title":"Reaction rates and mechanism of the ascorbic acid oxidation by molecular oxygen facilitated by cu(II)-containing amyloid-beta complexes and aggregates","volume":"114","author":"Jiang","year":"2010","journal-title":"J. Phys. Chem. B"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1007\/s12291-013-0375-3","article-title":"Vitamin c in disease prevention and cure: An overview","volume":"28","author":"Chambial","year":"2013","journal-title":"Indian J. Clin. Biochem. IJCB"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"761264","DOI":"10.1155\/2014\/761264","article-title":"Oxidative stress, prooxidants, and antioxidants: The interplay","volume":"2014","author":"Rahal","year":"2014","journal-title":"BioMed Res. Int."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/S0925-4439(01)00051-5","article-title":"Similarity of the yellow chromophores isolated from human cataracts with those from ascorbic acid-modified calf lens proteins: Evidence for ascorbic acid glycation during cataract formation","volume":"1537","author":"Cheng","year":"2001","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_108","first-page":"1007","article-title":"Does vitamin c act as a pro-oxidant under physiological conditions?","volume":"13","author":"Carr","year":"1999","journal-title":"FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.2174\/0929867053764635","article-title":"Metals, toxicity and oxidative stress","volume":"12","author":"Valko","year":"2005","journal-title":"Curr. Med. Chem."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.freeradbiomed.2003.11.004","article-title":"Cupric-amyloid beta peptide complex stimulates oxidation of ascorbate and generation of hydroxyl radical","volume":"36","author":"Dikalov","year":"2004","journal-title":"Free Radic. Biol. Med."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"17826","DOI":"10.1021\/ja805940m","article-title":"The amyloid-beta peptide of Alzheimer\u2019s disease binds Cu(I) in a linear Bis-His coordination environment: Insight into a possible neuroprotective mechanism for the amyloid-beta peptide","volume":"130","author":"Shearer","year":"2008","journal-title":"J. Am. Chem. Soc."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"11653","DOI":"10.1021\/bi8011093","article-title":"Amyloid beta-Cu2+ complexes in both monomeric and fibrillar forms do not generate H2O2 catalytically but quench hydroxyl radicals","volume":"47","author":"Nadal","year":"2008","journal-title":"Biochemistry"},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Huang, Y.N., Lai, C.C., Chiu, C.T., Lin, J.J., and Wang, J.Y. (2014). l-ascorbate attenuates the endotoxin-induced production of inflammatory mediators by inhibiting MAPK activation and NF-kappaB translocation in cortical neurons\/glia Cocultures. PloS ONE, 9.","DOI":"10.1371\/journal.pone.0097276"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"e1083","DOI":"10.1038\/cddis.2014.26","article-title":"High-dose of vitamin c supplementation reduces amyloid plaque burden and ameliorates pathological changes in the brain of 5XFAD mice","volume":"5","author":"Kook","year":"2014","journal-title":"Cell Death Dis."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1007\/s00702-014-1357-1","article-title":"Association of increased carotid intima-media thickness and lower plasma levels of vitamin C and vitamin E in old age subjects: Implications for Alzheimer\u2019s disease","volume":"122","author":"Polidori","year":"2015","journal-title":"J. Neural Transm."},{"key":"ref_116","first-page":"1","article-title":"Alzheimer\u2019s disease and endothelial dysfunction","volume":"31","author":"Bomboi","year":"2010","journal-title":"Neurol. Sci. Off. J. Ital. Neurol. Soc. Ital. Soc. Clin. Neurophysiol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.3109\/10715762.2010.508496","article-title":"Ascorbic acid prevents increased endothelial permeability caused by oxidized low density lipoprotein","volume":"44","author":"May","year":"2010","journal-title":"Free Radic. Res."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"2068","DOI":"10.1089\/ars.2013.5205","article-title":"Role of vitamin C in the function of the vascular endothelium","volume":"19","author":"May","year":"2013","journal-title":"Antioxid. Redox Signal."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3233\/JAD-2011-111034","article-title":"Bridging the pathophysiology of Alzheimer\u2019s disease with vascular pathology: The feed-back, the feed-forward, and oxidative stress","volume":"28","author":"Polidori","year":"2012","journal-title":"J. Alzheimers Dis."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.brainres.2008.06.124","article-title":"Hippocampal rage immunoreactivity in early and advanced Alzheimer\u2019s disease","volume":"1230","author":"Miller","year":"2008","journal-title":"Brain Res."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1038\/jcbfm.2009.277","article-title":"Ascorbic acid prevents blood-brain barrier disruption and sensory deficit caused by sustained compression of primary somatosensory cortex","volume":"30","author":"Lin","year":"2010","journal-title":"J. Cereb. Blood Flow Metab. Off. J. Int. Soc. Cereb. Blood Flow Metab."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/j.bbrc.2010.12.046","article-title":"Nitric oxide mediates tightening of the endothelial barrier by ascorbic acid","volume":"404","author":"May","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1097\/HJH.0b013e3280895b55","article-title":"Arterial stiffness as an independent predictor of longitudinal changes in cognitive function in the older individual","volume":"25","author":"Scuteri","year":"2007","journal-title":"J. Hypertens."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.numecd.2008.01.006","article-title":"Vitamin C consumption is associated with less progression in carotid intima media thickness in elderly men: A 3-year intervention study","volume":"19","author":"Ellingsen","year":"2009","journal-title":"Nutr. Metab. Cardiovasc. Dis. NMCD"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1007\/s00401-006-0115-3","article-title":"Rage, lrp-1, and amyloid-beta protein in Alzheimer\u2019s disease","volume":"112","author":"Donahue","year":"2006","journal-title":"Acta Neuropathol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.atherosclerosis.2007.06.011","article-title":"Intra-arterial vitamin C prevents endothelial dysfunction caused by ischemia-reperfusion","volume":"197","author":"Pleiner","year":"2008","journal-title":"Atherosclerosis"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/S0891-5849(96)00378-4","article-title":"Role of ascorbate and protein thiols in the release of nitric oxide from S-nitroso-albumin and S-nitroso-glutathione in human plasma","volume":"22","author":"Scorza","year":"1997","journal-title":"Free Radic. Biol. Med."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1111\/bcpt.12413","article-title":"Ascorbic acid reduces the adverse effects of delayed administration of tissue plasminogen activator in a rat stroke model","volume":"117","author":"Allahtavakoli","year":"2015","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"41","DOI":"10.5607\/en.2015.24.1.41","article-title":"Dehydroascorbic acid attenuates ischemic brain edema and neurotoxicity in cerebral ischemia: An in vivo study","volume":"24","author":"Song","year":"2015","journal-title":"Exp. Neurobiol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1111\/j.1463-1326.2008.00987.x","article-title":"Antioxidants attenuate hyperglycaemia-mediated brain endothelial cell dysfunction and blood-brain barrier hyperpermeability","volume":"11","author":"Allen","year":"2009","journal-title":"Diabetes Obes. Metab."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1002\/biof.1002","article-title":"Ascorbic acid, cognitive function, and Alzheimer\u2019s disease: A current review and future direction","volume":"38","author":"Bowman","year":"2012","journal-title":"BioFactors"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"93","DOI":"10.3233\/JAD-2009-0923","article-title":"Ascorbic acid and rates of cognitive decline in Alzheimer\u2019s disease","volume":"16","author":"Bowman","year":"2009","journal-title":"J. Alzheimers Dis."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1212\/01.wnl.0000262031.18018.1a","article-title":"Blood-brain barrier impairment in alzheimer disease: Stability and functional significance","volume":"68","author":"Bowman","year":"2007","journal-title":"Neurology"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/2045-8118-10-28","article-title":"Sustained choroid plexus function in human elderly and Alzheimer\u2019s disease patients","volume":"10","author":"Spector","year":"2013","journal-title":"Fluids Barriers CNS"},{"key":"ref_135","first-page":"99","article-title":"Lowered plasma vitamin C, but not vitamin E, concentrations in dementia patients","volume":"8","author":"Charlton","year":"2004","journal-title":"J. Nutr. Health Aging"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1016\/S0197-4580(03)00031-9","article-title":"Plasma antioxidants are similarly depleted in mild cognitive impairment and in Alzheimer\u2019s disease","volume":"24","author":"Rinaldi","year":"2003","journal-title":"Neurobiol. Aging"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1097\/00002093-199809000-00001","article-title":"Vitamin E and vitamin C supplement use and risk of incident Alzheimer disease","volume":"12","author":"Morris","year":"1998","journal-title":"Alzheimer Dis. Assoc. Disord."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1001\/archneur.61.1.82","article-title":"Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements: The cache county study","volume":"61","author":"Zandi","year":"2004","journal-title":"Arch. Neurol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1093\/aje\/kws202","article-title":"The association of antioxidants and cognition in the nurses\u2019 health study","volume":"177","author":"Devore","year":"2013","journal-title":"Am. J. Epidemiol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"3223","DOI":"10.1001\/jama.287.24.3223","article-title":"Dietary intake of antioxidants and risk of Alzheimer disease","volume":"287","author":"Engelhart","year":"2002","journal-title":"JAMA"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"309","DOI":"10.3233\/JAD-2003-5406","article-title":"Antioxidants in Alzheimer\u2019s disease-vitamin c delivery to a demanding brain","volume":"5","author":"Quinn","year":"2003","journal-title":"J. Alzheimers Dis."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"2009","DOI":"10.1345\/aph.1G280","article-title":"Dementia and Alzheimer\u2019s disease in community-dwelling elders taking vitamin C and\/or vitamin E","volume":"39","author":"Fillenbaum","year":"2005","journal-title":"Ann. Pharmacother."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"711","DOI":"10.3233\/JAD-2012-111853","article-title":"A critical review of vitamin C for the prevention of age-related cognitive decline and Alzheimer\u2019s disease","volume":"29","author":"Harrison","year":"2012","journal-title":"J. Alzheimers Dis."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1002\/nbm.1646","article-title":"Noninvasive quantification of ascorbate and glutathione concentration in the elderly human brain","volume":"24","author":"Emir","year":"2011","journal-title":"NMR Biomed."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"13669","DOI":"10.1074\/jbc.C113.464800","article-title":"Ascorbate induces ten-eleven translocation (Tet) methylcytosine dioxygenase-mediated generation of 5-hydroxymethylcytosine","volume":"288","author":"Minor","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"4887","DOI":"10.1002\/anie.201300399","article-title":"Maillard degradation pathways of vitamin C","volume":"52","author":"Smuda","year":"2013","journal-title":"Angew. Chem."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/9\/7\/670\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:40:37Z","timestamp":1760208037000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/9\/7\/670"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,6,27]]},"references-count":146,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2017,7]]}},"alternative-id":["nu9070670"],"URL":"https:\/\/doi.org\/10.3390\/nu9070670","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,6,27]]}}}