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The majority of early-onset familial AD (EOfAD) cases involve dominant mutations in the gene PSEN1. PSEN1 null mutations do not cause EOfAD. We exploited putative hypomorphic and EOfAD-like mutations in the zebrafish psen1 gene to explore the effects of age and genotype on brain responses to acute hypoxia. Both mutations accelerate age-dependent changes in hypoxia-sensitive gene expression supporting that ageing is necessary, but insufficient, for AD occurrence. Curiously, the responses to acute hypoxia become inverted in extremely aged fish. This is associated with an apparent inability to upregulate glycolysis. Wild-type PSEN1 allele expression is reduced in post-mortem brains of human EOfAD mutation carriers (and extremely aged fish), possibly contributing to EOfAD pathogenesis. We also observed that age-dependent loss of HIF1 stabilization under hypoxia is a phenomenon conserved across vertebrate classes.<\/jats:p>","DOI":"10.1093\/hmg\/ddaa119","type":"journal-article","created":{"date-parts":[[2020,6,16]],"date-time":"2020-06-16T07:09:27Z","timestamp":1592291367000},"page":"2379-2394","source":"Crossref","is-referenced-by-count":15,"title":["Accelerated loss of hypoxia response in zebrafish with familial Alzheimer\u2019s disease-like mutation of presenilin 1"],"prefix":"10.1093","volume":"29","author":[{"given":"Morgan","family":"Newman","sequence":"first","affiliation":[{"name":"School of Biological Sciences, University of Adelaide, Adelaide, South Australia 5005, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hani Moussavi","family":"Nik","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, University of Adelaide, Adelaide, South Australia 5005, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg T","family":"Sutherland","sequence":"additional","affiliation":[{"name":"Discipline of Pathology, School of Medical Sciences and Charles Perkins Centre, Faculty of Medicine and Health, The University of Sydney, Camperdown, New South Wales 2006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nhi","family":"Hin","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, University of Adelaide, Adelaide, South Australia 5005, Australia"},{"name":"Bioinformatics Hub, University of Adelaide, Adelaide, South Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woojin S","family":"Kim","sequence":"additional","affiliation":[{"name":"Brain and Mind Centre, Central Clinical School, Faculty of Medicine and Health, The University of Sydney, Camperdown, New South Wales 2052, Australia"},{"name":"School of Medical Sciences, University of New South Wales and Neuroscience Research Australia, Randwick, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glenda M","family":"Halliday","sequence":"additional","affiliation":[{"name":"Brain and Mind Centre, Central Clinical School, Faculty of Medicine and Health, The University of Sydney, Camperdown, New South Wales 2052, Australia"},{"name":"School of Medical Sciences, University of New South Wales and Neuroscience Research Australia, Randwick, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suman","family":"Jayadev","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Washington, Seattle, Washington 98195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carole","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Washington, Seattle, Washington 98195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela S","family":"Laird","sequence":"additional","affiliation":[{"name":"Centre for MND Research, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, New South Wales 2109, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitlin W","family":"Lucas","sequence":"additional","affiliation":[{"name":"Centre for MND Research, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, New South Wales 2109, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thaksaon","family":"Kittipassorn","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, University of Adelaide, Adelaide, South Australia 5005, Australia"},{"name":"Department of Physiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan J","family":"Peet","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, University of Adelaide, Adelaide, South Australia 5005, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Lardelli","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, University of Adelaide, Adelaide, South Australia 5005, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,6,26]]},"reference":[{"key":"2021070119200797700_ref1","doi-asserted-by":"crossref","first-page":"1774","DOI":"10.1126\/science.1197623","article-title":"Decreased clearance of CNS beta-amyloid in Alzheimer's 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Alzheimers Dis."},{"key":"2021070119200797700_ref26","doi-asserted-by":"crossref","first-page":"533","DOI":"10.3389\/fnins.2018.00533","article-title":"Dysregulation of neuronal iron homeostasis as an alternative unifying effect of mutations causing familial Alzheimer's disease","volume":"12","author":"Lumsden","year":"2018","journal-title":"Front. Neurosci."},{"key":"2021070119200797700_ref27","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1001\/jamaneurol.2015.1099","article-title":"Brain imaging and blood biomarker abnormalities in children with autosomal dominant Alzheimer disease: a cross-sectional study","volume":"72","author":"Quiroz","year":"2015","journal-title":"JAMA Neurol."},{"key":"2021070119200797700_ref28","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1016\/S1474-4422(12)70228-4","article-title":"Brain imaging and fluid biomarker analysis in young adults at genetic risk for autosomal dominant Alzheimer's disease in the presenilin 1 E280A kindred: a case-control study","volume":"11","author":"Reiman","year":"2012","journal-title":"Lancet Neurol."},{"key":"2021070119200797700_ref29","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/S1474-4422(18)30028-0","article-title":"Spatial patterns of neuroimaging biomarker change in individuals from families with autosomal dominant Alzheimer's disease: a longitudinal study","volume":"17","author":"Gordon","year":"2018","journal-title":"Lancet Neurol."},{"key":"2021070119200797700_ref30","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/s13041-019-0467-y","article-title":"Brain transcriptome analysis of a familial Alzheimer\u2019s disease-like mutation in the zebrafish presenilin 1 gene implies effects on energy production","volume":"12","year":"2019","journal-title":"Mol Brain"},{"key":"2021070119200797700_ref31","doi-asserted-by":"crossref","first-page":"e0227258","DOI":"10.1371\/journal.pone.0227258","article-title":"Accelerated brain aging towards transcriptional inversion in a zebrafish model of the K115fs mutation of human PSEN2","volume":"15","author":"Hin","year":"2020","journal-title":"PLoS One"},{"key":"2021070119200797700_ref32","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1002\/acn3.755","article-title":"Alternative splicing in a presenilin 2 variant associated with Alzheimer disease","volume":"6","author":"Braggin","year":"2019","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"2021070119200797700_ref33","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/sj.embor.7400897","article-title":"Loss-of-function presenilin mutations in Alzheimer disease. Talking point on the role of presenilin mutations in Alzheimer disease","volume":"8","author":"De Strooper","year":"2007","journal-title":"EMBO Rep."},{"key":"2021070119200797700_ref34","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1126\/science.1196284","article-title":"Gamma-secretase gene mutations in familial acne inversa","volume":"330","author":"Wang","year":"2010","journal-title":"Science"},{"key":"2021070119200797700_ref35","doi-asserted-by":"crossref","first-page":"1810","DOI":"10.2353\/ajpath.2009.090219","article-title":"Presenilins are enriched in endoplasmic reticulum membranes associated with mitochondria","volume":"175","author":"Area-Gomez","year":"2009","journal-title":"Am. J. 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Neurodegener."},{"key":"2021070119200797700_ref38","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1016\/j.celrep.2014.07.028","article-title":"Nontranscriptional role of Hif-1alpha in activation of gamma-secretase and notch signaling in breast cancer","volume":"8","author":"Villa","year":"2014","journal-title":"Cell Rep."},{"key":"2021070119200797700_ref39","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1038\/nrc704","article-title":"Hypoxia--a key regulatory factor in tumour growth","volume":"2","author":"Harris","year":"2002","journal-title":"Nat. Rev. Cancer"},{"key":"2021070119200797700_ref40","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.cmet.2006.02.002","article-title":"HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia","volume":"3","author":"Kim","year":"2006","journal-title":"Cell Metab."},{"key":"2021070119200797700_ref41","doi-asserted-by":"crossref","first-page":"13464","DOI":"10.18632\/oncotarget.7229","article-title":"Targeting hypoxic response for cancer therapy","volume":"7","author":"Paolicchi","year":"2016","journal-title":"Oncotarget"},{"key":"2021070119200797700_ref42","doi-asserted-by":"crossref","first-page":"2076","DOI":"10.1002\/1873-3468.12237","article-title":"The tumor suppressor gene lkb1 is essential for glucose homeostasis during zebrafish early development","volume":"590","author":"Kuang","year":"2016","journal-title":"FEBS Lett."},{"key":"2021070119200797700_ref43","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/S0304-3940(01)01630-5","article-title":"Energetic metabolism in mouse cerebral cortex during chronic hypoxia","volume":"301","author":"Caceda","year":"2001","journal-title":"Neurosci. Lett."},{"key":"2021070119200797700_ref44","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1016\/S0531-5565(02)00088-8","article-title":"Life spans and senescent phenotypes in two strains of Zebrafish (Danio rerio)","volume":"37","author":"Gerhard","year":"2002","journal-title":"Exp. Gerontol."},{"key":"2021070119200797700_ref45","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1146\/annurev-genet-112414-054639","article-title":"Nonsense-mediated mRNA decay: degradation of defective transcripts is only part of the story","volume":"49","author":"He","year":"2015","journal-title":"Annu. Rev. Genet."},{"key":"2021070119200797700_ref46","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1038\/s41586-019-1064-z","article-title":"Genetic compensation triggered by mutant mRNA degradation","volume":"568","author":"El-Brolosy","year":"2019","journal-title":"Nature"},{"key":"2021070119200797700_ref47","doi-asserted-by":"crossref","first-page":"R158","DOI":"10.1152\/ajpregu.90829.2008","article-title":"Increased prolyl 4-hydroxylase expression and differential regulation of hypoxia-inducible factors in the aged rat brain","volume":"297","author":"Ndubuizu","year":"2009","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"2021070119200797700_ref48","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.brainres.2010.09.064","article-title":"Hypoxia-inducible factor-1 (HIF-1)-independent microvascular angiogenesis in the aged rat brain","volume":"1366","author":"Ndubuizu","year":"2010","journal-title":"Brain Res."},{"key":"2021070119200797700_ref49","doi-asserted-by":"crossref","first-page":"2275","DOI":"10.1093\/molbev\/msi225","article-title":"Molecular phylogeny and divergence times of deuterostome animals","volume":"22","author":"Blair","year":"2005","journal-title":"Mol. Biol. Evol."},{"key":"2021070119200797700_ref50","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1038\/nature02661","article-title":"Gene regulation and DNA damage in the ageing human brain","volume":"429","author":"Lu","year":"2004","journal-title":"Nature"},{"key":"2021070119200797700_ref51","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1126\/science.aaf6846","article-title":"ATP as a biological hydrotrope","volume":"356","author":"Patel","year":"2017","journal-title":"Science"},{"key":"2021070119200797700_ref52","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1038\/s41593-019-0471-7","article-title":"Common brain disorders are associated with heritable patterns of apparent aging of the brain","volume":"22","author":"Kaufmann","year":"2019","journal-title":"Nat. Neurosci."},{"key":"2021070119200797700_ref53","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/0197-4580(92)90076-A","article-title":"Reduced temporal lobe blood flow in Alzheimer's disease","volume":"13","author":"Eberling","year":"1992","journal-title":"Neurobiol. Aging"},{"key":"2021070119200797700_ref54","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1212\/WNL.50.6.1563","article-title":"Preclinical prediction of Alzheimer's disease using SPECT","volume":"50","author":"Johnson","year":"1998","journal-title":"Neurology"},{"key":"2021070119200797700_ref55","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.nbd.2018.07.009","article-title":"Hypoxia promotes tau hyperphosphorylation with associated neuropathology in vascular dysfunction","volume":"126","author":"Raz","year":"2019","journal-title":"Neurobiol. Dis."},{"key":"2021070119200797700_ref56","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/S0896-6273(00)81109-5","article-title":"Neuroplasticity failure in Alzheimer's disease: bridging the gap between plaques and tangles","volume":"24","author":"Mesulam","year":"1999","journal-title":"Neuron"},{"key":"2021070119200797700_ref57","doi-asserted-by":"crossref","first-page":"1961","DOI":"10.1016\/j.neurobiolaging.2014.03.031","article-title":"Brain gene expression patterns differentiate mild cognitive impairment from normal aged and Alzheimer's disease","volume":"35","author":"Berchtold","year":"2014","journal-title":"Neurobiol. Aging"},{"key":"2021070119200797700_ref58","doi-asserted-by":"crossref","first-page":"61","DOI":"10.3233\/JAD-2007-11110","article-title":"Possible compensatory events in adult down syndrome brain prior to the development of Alzheimer disease neuropathology: targets for nonpharmacological intervention","volume":"11","author":"Head","year":"2007","journal-title":"J. Alzheimers Dis."},{"key":"2021070119200797700_ref59","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1016\/j.nicl.2017.12.037","article-title":"Metabolic brain networks in aging and preclinical Alzheimer's disease","volume":"17","author":"Arnemann","year":"2018","journal-title":"Neuroimage Clin."},{"key":"2021070119200797700_ref60","doi-asserted-by":"crossref","first-page":"3662","DOI":"10.1093\/hmg\/ddv110","article-title":"Alzheimer's disease-related peptide PS2V plays ancient, conserved roles in suppression of the unfolded protein response under hypoxia and stimulation of gamma-secretase activity","volume":"24","author":"Moussavi Nik","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"2021070119200797700_ref61","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1046\/j.1471-4159.1999.0722498.x","article-title":"A novel presenilin-2 splice variant in human Alzheimer's disease brain tissue","volume":"72","author":"Sato","year":"1999","journal-title":"J. Neurochem."},{"key":"2021070119200797700_ref62","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.jchemneu.2003.12.004","article-title":"Induction of neuronal death by ER stress in Alzheimer's disease","volume":"28","author":"Katayama","year":"2004","journal-title":"J. Chem. Neuroanat."},{"key":"2021070119200797700_ref63","doi-asserted-by":"crossref","first-page":"11606","DOI":"10.1523\/JNEUROSCI.0954-13.2013","article-title":"Trans-dominant negative effects of pathogenic PSEN1 mutations on gamma-secretase activity and Abeta production","volume":"33","author":"Heilig","year":"2013","journal-title":"J. Neurosci."},{"key":"2021070119200797700_ref64","doi-asserted-by":"crossref","first-page":"3356","DOI":"10.15252\/embj.201796797","article-title":"Increased localization of APP-C99 in mitochondria-associated ER membranes causes mitochondrial dysfunction in Alzheimer disease","volume":"36","author":"Pera","year":"2017","journal-title":"EMBO J."},{"key":"2021070119200797700_ref65","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/S0006-8993(96)01274-7","article-title":"Expression of presenilin-1 and -2 mRNAs in rat and Alzheimer's disease brains","volume":"748","author":"Takami","year":"1997","journal-title":"Brain Res."},{"key":"2021070119200797700_ref66","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1111\/j.1468-1331.1999.tb00009.x","article-title":"Alteration in brain presenilin-1 mRNA expression in sporadic Alzheimer's disease","volume":"6","author":"Isoe-Wada","year":"1999","journal-title":"Eur. J. Neurol."},{"key":"2021070119200797700_ref67","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1159\/000017246","article-title":"The expression of presenilin 1 mRNA in skin fibroblasts and brains from sporadic Alzheimer's disease","volume":"11","author":"Ikeda","year":"2000","journal-title":"Dement. Geriatr. Cogn. Disord."},{"key":"2021070119200797700_ref68","doi-asserted-by":"crossref","first-page":"771","DOI":"10.3233\/JAD-2010-100729","article-title":"Upregulation of presenilin 1 in brains of sporadic, late-onset Alzheimer's disease","volume":"22","author":"Borghi","year":"2010","journal-title":"J. Alzheimers Dis."},{"key":"2021070119200797700_ref69","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3233\/JAD-160160","article-title":"Gene expression of quaking in sporadic Alzheimer's disease patients is both upregulated and related to expression levels of genes involved in amyloid plaque and neurofibrillary tangle formation","volume":"53","author":"Farnsworth","year":"2016","journal-title":"J. Alzheimers Dis."},{"key":"2021070119200797700_ref70","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/0014-5793(96)00969-6","article-title":"Quantification of presenilin-1 mRNA in Alzheimer's disease brains","volume":"394","author":"Johnston","year":"1996","journal-title":"FEBS Lett."},{"key":"2021070119200797700_ref71","doi-asserted-by":"crossref","first-page":"757","DOI":"10.3233\/JAD-140033","article-title":"PSEN1 and PSEN2 gene expression in Alzheimer's disease brain: a new approach","volume":"42","author":"Delabio","year":"2014","journal-title":"J. Alzheimers Dis."},{"key":"2021070119200797700_ref72","doi-asserted-by":"crossref","first-page":"933","DOI":"10.3233\/JAD-171037","article-title":"Aging without dementia is achievable: current evidence from epidemiological research","volume":"62","author":"Qiu","year":"2018","journal-title":"J. Alzheimers Dis."},{"key":"2021070119200797700_ref73","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1212\/WNL.60.3.477","article-title":"Mild cognitive impairment in the oldest old","volume":"60","author":"Boeve","year":"2003","journal-title":"Neurology"},{"key":"2021070119200797700_ref74","doi-asserted-by":"crossref","first-page":"P152","DOI":"10.1093\/geronb\/56.3.P152","article-title":"Dementia is not inevitable: a population-based study of Danish centenarians","volume":"56","author":"Andersen-Ranberg","year":"2001","journal-title":"J. Gerontol. B Psychol. Sci. Soc. Sci."},{"key":"2021070119200797700_ref75","article-title":"Iron responsive element (IRE)-mediated responses to iron dyshomeostasis in Alzheimer\u2019s disease","author":"Hin","year":"2020","journal-title":"bioRxiv"},{"key":"2021070119200797700_ref76","doi-asserted-by":"crossref","first-page":"2061","DOI":"10.1002\/glia.22726","article-title":"Excitotoxic brain injury in adult zebrafish stimulates neurogenesis and long-distance neuronal integration","volume":"62","author":"Skaggs","year":"2014","journal-title":"Glia"},{"key":"2021070119200797700_ref77","doi-asserted-by":"crossref","first-page":"e0118956","DOI":"10.1371\/journal.pone.0118956","article-title":"Granulin knock out zebrafish lack frontotemporal lobar degeneration and neuronal ceroid lipofuscinosis pathology","volume":"10","author":"Solchenberger","year":"2015","journal-title":"PLoS One"},{"key":"2021070119200797700_ref78","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1016\/j.molcel.2011.08.033","article-title":"Oxygen-dependent cleavage of the p75 neurotrophin receptor triggers stabilization of HIF-1alpha","volume":"44","author":"Le Moan","year":"2011","journal-title":"Mol. Cell"},{"key":"2021070119200797700_ref79","doi-asserted-by":"crossref","first-page":"1926","DOI":"10.1172\/JCI31370","article-title":"Regulation of iron homeostasis by the hypoxia-inducible transcription factors (HIFs)","volume":"117","author":"Peyssonnaux","year":"2007","journal-title":"J. Clin. Invest."},{"key":"2021070119200797700_ref80","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1016\/j.bbamcr.2015.01.021","article-title":"Cellular iron uptake, trafficking and metabolism: key molecules and mechanisms and their roles in disease","volume":"1853","author":"Lane","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"2021070119200797700_ref81","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.51031","article-title":"Impaired lysosomal acidification triggers iron deficiency and inflammation in vivo","volume":"8","author":"Yambire","year":"2019","journal-title":"Elife"},{"key":"2021070119200797700_ref82","doi-asserted-by":"crossref","DOI":"10.1016\/j.jalz.2018.06.3059","article-title":"Relationship between physical activity, cognition, and Alzheimer pathology in autosomal dominant Alzheimer's disease","volume":"14","author":"Muller","year":"2018","journal-title":"Alzheimers Dement."},{"key":"2021070119200797700_ref83","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1016\/j.mayocp.2016.04.024","article-title":"Physical activity and Alzheimer disease: a protective association","volume":"91","author":"Santos-Lozano","year":"2016","journal-title":"Mayo Clin. Proc."},{"key":"2021070119200797700_ref84","first-page":"733","article-title":"Physical activity and Alzheimer's disease: a systematic review","volume":"72","author":"Stephen","year":"2017","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"2021070119200797700_ref85","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1186\/1471-2458-14-643","article-title":"Epidemiologic studies of modifiable factors associated with cognition and dementia: systematic review and meta-analysis","volume":"14","author":"Beydoun","year":"2014","journal-title":"BMC Public Health"},{"key":"2021070119200797700_ref86","doi-asserted-by":"crossref","first-page":"359","DOI":"10.3233\/JAD-170567","article-title":"Effects of physical exercise on Alzheimer's disease biomarkers: a systematic review of intervention studies","volume":"61","author":"Frederiksen","year":"2018","journal-title":"J. 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