Role of Retinoid X Receptors (RXRs) and dietary vitamin A in Alzheimer's disease: Evidence from clinicopathological and preclinical studies

Adams, 2010, The neurobehavioral teratology of retinoids: a 50-year history, Birth Defects Res. A, 88, 895, 10.1002/bdra.20721 Arfaoui, 2013, Expression of retinoic acid receptors and retinoid X receptors in normal and vitamin A deficient adult rat brain, Ann. Anat., 195, 111, 10.1016/j.aanat.2012.06.006 Arsenault, 2013, PAK inactivation impairs social recognition in 3xTg-AD Mice without increasing brain deposition of Tau and Abeta, J. Neurosci., 33, 10729, 10.1523/JNEUROSCI.1501-13.2013 Asson-Batres, 2014 Bachmeier, 2013, Stimulation of the retinoid X receptor facilitates beta-amyloid clearance across the blood-brain barrier, J. Mol. Neurosci., 49, 270, 10.1007/s12031-012-9866-6 Bah, 2016, Modulation of intrinsically disordered protein function by post-translational modifications, J. Biol. Chem., 291, 6696, 10.1074/jbc.R115.695056 Ballard, 2011, Alzheimer's disease, Lancet, 377, 1019, 10.1016/S0140-6736(10)61349-9 Behairi, 2016, All-trans retinoic acid (ATRA) prevents lipopolysaccharide-induced neuroinflammation, amyloidogenesis and memory impairment in aged rats, J. Neuroimmunol., 300, 21, 10.1016/j.jneuroim.2016.10.004 Bennett, 2002, Natural history of mild cognitive impairment in older persons, Neurology, 59, 198, 10.1212/WNL.59.2.198 Bennett, 2005, Mild cognitive impairment is related to Alzheimer disease pathology and cerebral infarctions, Neurology, 64, 834, 10.1212/01.WNL.0000152982.47274.9E Bennett, 2006, Decision rules guiding the clinical diagnosis of Alzheimer's disease in two community-based cohort studies compared to standard practice in a clinic-based cohort study, Neuroepidemiology, 27, 169, 10.1159/000096129 Bennett, 2006, Neuropathology of older persons without cognitive impairment from two community-based studies, Neurology, 66, 1837, 10.1212/01.wnl.0000219668.47116.e6 Bennett, 2012, Overview and findings from the religious orders study, Curr. Alzheimer Res., 9, 628, 10.2174/156720512801322573 Bennett, 2012, Relation of neuropathology to cognition in persons without cognitive impairment, Ann. Neurol., 72, 599, 10.1002/ana.23654 Bennett, 2018, Religious orders study and rush memory and aging project, J. Alzheimers Dis., 64, S161, 10.3233/JAD-179939 Blomhoff, 2006, Overview of retinoid metabolism and function, J. Neurobiol., 66, 606, 10.1002/neu.20242 Bonhomme, 2014, Vitamin A status regulates glucocorticoid availability in Wistar rats: consequences on cognitive functions and hippocampal neurogenesis?, Front. Behav. Neurosci., 8, 20, 10.3389/fnbeh.2014.00020 Bonhomme, 2014, Retinoic acid modulates intrahippocampal levels of corticosterone in middle-aged mice: consequences on hippocampal plasticity and contextual memory, Front. Aging Neurosci., 6, 6, 10.3389/fnagi.2014.00006 Bories, 2012, Sex-dependent alterations in social behaviour and cortical synaptic activity coincide at different ages in a model of Alzheimer’s disease, PLoS One, 7, 10.1371/journal.pone.0046111 Bourassa, 2019, Transferrin receptor-mediated uptake at the blood-brain barrier is not impaired by Alzheimer's disease neuropathology, Mol. Pharm., 16, 583, 10.1021/acs.molpharmaceut.8b00870 Bourassa, 2019, Beta-amyloid pathology in human brain microvessel extracts from the parietal cortex: relation with cerebral amyloid angiopathy and Alzheimer's disease, Acta Neuropathol., 137, 801, 10.1007/s00401-019-01967-4 Bourassa, 2020, Brain mural cell loss in the parietal cortex in Alzheimer's disease correlates with cognitive decline and TDP-43 pathology, Neuropathol. Appl. Neurobiol., 37, 201 Bourdel-Marchasson, 2001, Antioxidant defences and oxidative stress markers in erythrocytes and plasma from normally nourished elderly Alzheimer patients, Age Ageing, 30, 235, 10.1093/ageing/30.3.235 Braak, 1991, Neuropathological stageing of Alzheimer-related changes, Acta Neuropathol., 82, 239, 10.1007/BF00308809 Brossaud, 2017, Retinoic acid increases glucocorticoid receptor phosphorylation via cyclin-dependent kinase 5, Mol. Cell. Neurosci., 82, 96, 10.1016/j.mcn.2017.05.001 Brtko, 2007, Age-related change in the retinoid X receptor beta gene expression in peripheral blood mononuclear cells of healthy volunteers: effect of 13-cis retinoic acid supplementation, Mech. Ageing Dev., 128, 594, 10.1016/j.mad.2007.08.005 Chakrabarti, 2016, Molecular signaling mechanisms of natural and synthetic retinoids for inhibition of pathogenesis in Alzheimer's disease, J. Alzheimers Dis., 50, 335, 10.3233/JAD-150450 Cheng, 2008, Retinoic acid (RA) regulates 17beta-hydroxysteroid dehydrogenase type 2 expression in endometrium: interaction of RA receptors with specificity protein (SP) 1/SP3 for estradiol metabolism, J. Clin. Endocrinol. Metab., 93, 1915, 10.1210/jc.2007-1536 Corcoran, 2004, Disruption of the retinoid signalling pathway causes a deposition of amyloid beta in the adult rat brain, Eur. J. Neurosci., 20, 896, 10.1111/j.1460-9568.2004.03563.x Crandall, 2004, 13-cis-retinoic acid suppresses hippocampal cell division and hippocampal-dependent learning in mice, Proc. Natl. Acad. Sci. U. S. A., 101, 5111, 10.1073/pnas.0306336101 Cuadrado-Tejedor, 2011, Chronic mild stress in mice promotes cognitive impairment and CDK5-dependent Tau hyperphosphorylation, Behav. Brain Res., 220, 338, 10.1016/j.bbr.2011.01.005 Cummings, 2016, Double-blind, placebo-controlled, proof-of-concept trial of bexarotene Xin moderate Alzheimer’s disease, Alzheimers Res. Ther., 8, 4, 10.1186/s13195-016-0173-2 D'Ambrosio, 2011, Vitamin A metabolism: an update, Nutrients, 3, 63, 10.3390/nu3010063 Damdimopoulou, 2019, Retinoic acid signaling in ovarian folliculogenesis and steroidogenesis, Reprod. Toxicol., 87, 32, 10.1016/j.reprotox.2019.04.007 de Oliveira, 2015, The neurotoxic effects of vitamin A and retinoids, An. Acad. Bras. Cienc., 87, 1361, 10.1590/0001-3765201520140677 Dellu, 2000, Genetic differences in response to novelty and spatial memory using a two-trial recognition task in mice, Neurobiol. Learn. Mem., 73, 31, 10.1006/nlme.1999.3919 Desikan, 2008, MRI measures of temporoparietal regions show differential rates of atrophy during prodromal AD, Neurology, 71, 819, 10.1212/01.wnl.0000320055.57329.34 Desikan, 2009, Temporoparietal MR imaging measures of atrophy in subjects with mild cognitive impairment that predict subsequent diagnosis of Alzheimer disease, AJNR Am. J. Neuroradiol., 30, 532, 10.3174/ajnr.A1397 Ding, 2008, Retinoic acid attenuates beta-amyloid deposition and rescues memory deficits in an Alzheimer's disease transgenic mouse model, J. Neurosci., 28, 11622, 10.1523/JNEUROSCI.3153-08.2008 Dumetz, 2019, Normalization of hippocampal retinoic acid level corrects age-related memory deficits in rats, Neurobiol. Aging Enderlin, 1997, Aging decreases the abundance of retinoic acid (RAR) and triiodothyronine (TR) nuclear receptor mRNA in rat brain: effect of the administration of retinoids, FEBS Lett., 412, 629, 10.1016/S0014-5793(97)00845-4 Enderlin, 1997, Age-related decreases in mRNA for brain nuclear receptors and target genes are reversed by retinoic acid treatment, Neurosci. Lett., 229, 125, 10.1016/S0304-3940(97)00424-2 Endres, 2014, Increased CSF APPs-α levels in patients with Alzheimer disease treated with acitretin, Neurology, 83, 1930, 10.1212/WNL.0000000000001017 Etchamendy, 2001, Alleviation of a selective age-related relational memory deficit in mice by pharmacologically induced normalization of brain retinoid signaling, J. Neurosci., 21, 6423, 10.1523/JNEUROSCI.21-16-06423.2001 Etchamendy, 2003, Vitamin A deficiency and relational memory deficit in adult mice: relationships with changes in brain retinoid signalling, Behav. Brain Res., 145, 37, 10.1016/S0166-4328(03)00099-8 Feart, 2005, Differential effect of retinoic acid and triiodothyronine on the age-related hypo-expression of neurogranin in rat, Neurobiol. Aging, 26, 729, 10.1016/j.neurobiolaging.2004.06.004 Feart, 2005, Aging affects the retinoic acid and the triiodothyronine nuclear receptor mRNA expression in human peripheral blood mononuclear cells, Eur. J. Endocrinol., 152, 449, 10.1530/eje.1.01858 Finch, 2014, The menopause and aging, a comparative perspective, J. Steroid Biochem. Mol. Biol., 142, 132, 10.1016/j.jsbmb.2013.03.010 Georgiades, 1998, Regulation of retinoid X receptor-gamma gene transcript levels in rat heart cells, Cell Biol. Int., 22, 457, 10.1006/cbir.1998.0282 Goncalves, 2013, Amyloid beta inhibits retinoic acid synthesis exacerbating Alzheimer disease pathology which can be attenuated by an retinoic acid receptor alpha agonist, Eur. J. Neurosci., 37, 1182, 10.1111/ejn.12142 Goodman, 2006, Retinoid receptors, transporters, and metabolizers as therapeutic targets in late onset Alzheimer disease, J. Cell. Physiol., 209, 598, 10.1002/jcp.20784 Harrison, 2012, Mechanisms involved in the intestinal absorption of dietary vitamin A and provitamin A carotenoids, Biochim. Biophys. Acta, 1821, 70, 10.1016/j.bbalip.2011.06.002 Hirata-Fukae, 2008, Females exhibit more extensive amyloid, but not Tau, pathology in an Alzheimer transgenic model, Brain Res., 1216, 92, 10.1016/j.brainres.2008.03.079 Holthoewer, 2012, Acitretin, an enhancer of alpha-secretase expression, crosses the blood-brain barrier and is not eliminated by P-glycoprotein, Neurodegener. Dis., 10, 224, 10.1159/000334300 Huang, 2011, Retinoid X receptor gamma signaling accelerates CNS remyelination, Nat. Neurosci., 14, 45, 10.1038/nn.2702 Huang, 2018, Diminished circulating retinol and elevated α-TOH/retinol ratio predict an increased risk of cognitive decline in aging Chinese adults, especially in subjects with ApoE2 or ApoE4 genotype, Aging (Albany NY), 10, 4066, 10.18632/aging.101694 Idres, 2002, Activation of retinoic acid receptor-dependent transcription by all-trans-retinoic acid metabolites and isomers, J. Biol. Chem., 277, 31491, 10.1074/jbc.M205016200 Jarvis, 2010, Retinoic acid receptor-alpha signalling antagonizes both intracellular and extracellular amyloid-beta production and prevents neuronal cell death caused by amyloid-beta, Eur. J. Neurosci., 32, 1246, 10.1111/j.1460-9568.2010.07426.x Kapoor, 2013, Retinoic acid-elicited RARα/RXRα signaling attenuates Aβ production by directly inhibiting γ-secretase-mediated cleavage of amyloid precursor protein, ACS Chem. Neurosci., 4, 1093, 10.1021/cn400039s King, 2018, Age-related changes in the spatial frequency threshold of male and female 3xTg-AD mice using OptoMotry, J. Alzheimers Dis., 62, 591, 10.3233/JAD-170805 Kitaoka, 2013, The retinoic acid receptor agonist Am80 increases hippocampal ADAM10 in aged SAMP8 mice, Neuropharmacology, 72, 58, 10.1016/j.neuropharm.2013.04.009 Koryakina, 2009, Regulation of secretases by all-trans-retinoic acid, FEBS J., 276, 2645, 10.1111/j.1742-4658.2009.06992.x Krezel, 2019, Alternative retinoid X receptor (RXR) ligands, Mol. Cell. Endocrinol., 491, 110436, 10.1016/j.mce.2019.04.016 Lane, 2005, Role of retinoid signalling in the adult brain, Prog. Neurobiol., 75, 275, 10.1016/j.pneurobio.2005.03.002 Lee, 2009, All-trans retinoic acid as a novel therapeutic strategy for Alzheimer’s disease, Expert. Rev. Neurother., 9, 1615, 10.1586/ern.09.86 Leotsinidis, 2000, Plasma retinol and tocopherol levels in greek elderly population from an urban and a rural area: associations with the dietary habits, Eur. J. Epidemiol., 16, 1009, 10.1023/A:1010895227352 Lerner, 2012, Retinoids for treatment of Alzheimer's disease, Biofactors, 38, 84, 10.1002/biof.196 Letondor, 2016, EPA/DHA and Vitamin A supplementation improves spatial memory and alleviates the age-related decrease in hippocampal RXRgamma and kinase expression in rats, Front. Aging Neurosci., 8, 103, 10.3389/fnagi.2016.00103 Li, 2014, The multifaceted nature of retinoid transport and metabolism, Hepatobiliary Surg. Nutr., 3, 126 Li, 2015, Ectopic cross-talk between thyroid and retinoic acid signaling: a possible etiology for spinal neural tube defects, Gene, 573, 254, 10.1016/j.gene.2015.07.048 Liu, 1993, The mouse retinoid-X receptor-gamma gene: genomic organization and evidence for functional isoforms, Mol. Endocrinol., 7, 651 Lopes da Silva, 2014, Plasma nutrient status of patients with Alzheimer’s disease: systematic review and meta-analysis, Alzheimers Dement., 10, 485, 10.1016/j.jalz.2013.05.1771 Lopez-Teros, 2014, International experiences in assessing vitamin A status and applying the vitamin A-labeled isotope dilution method, Int. J. Vitam. Nutr. Res., 84, 40, 10.1024/0300-9831/a000184 Marissal-Arvy, 2013, Vitamin A regulates hypothalamic-pituitary-adrenal axis status in LOU/C rats, J. Endocrinol., 219, 21, 10.1530/JOE-13-0062 Markesbery, 2006, Neuropathologic substrate of mild cognitive impairment, Arch. Neurol., 63, 38, 10.1001/archneur.63.1.38 McCaffery, 2003, Too much of a good thing: retinoic acid as an endogenous regulator of neural differentiation and exogenous teratogen, Eur. J. Neurosci., 18, 457, 10.1046/j.1460-9568.2003.02765.x Mdzomba, 2018, Nogo-A inactivation improves visual plasticity and recovery after retinal injury, Cell Death Dis., 9, 727, 10.1038/s41419-018-0780-x Mey, 2004, Retinoic acid signaling in the nervous system of adult vertebrates, Neuroscientist, 10, 409, 10.1177/1073858404263520 Mingaud, 2008, Retinoid hyposignaling contributes to aging-related decline in hippocampal function in short-term/working memory organization and long-term declarative memory encoding in mice, J. Neurosci., 28, 279, 10.1523/JNEUROSCI.4065-07.2008 Mirra, 1991, The consortium to establish a registry for Alzheimer's disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer's disease, Neurology, 41, 479, 10.1212/WNL.41.4.479 Montine, 2012, National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease: a practical approach, Acta Neuropathol., 10.1007/s00401-011-0910-3 Moodley, 2015, Diagnostic differentiation of mild cognitive impairment due to Alzheimer's disease using a hippocampus-dependent test of spatial memory, Hippocampus, 25, 939, 10.1002/hipo.22417 Moutinho, 2017, Therapeutic potential of nuclear receptor agonists in Alzheimer's disease, J. Lipid Res., 58, 1937, 10.1194/jlr.R075556 Muñoz-Cabrera, 2019, Bexarotene therapy ameliorates behavioral deficits and induces functional and molecular changes in very-old Triple Transgenic Mice model of Alzheimer’s disease, PLoS One, 14, 10.1371/journal.pone.0223578 Navigatore Fonzo, 2013, Retinoic acid receptors move in time with the clock in the hippocampus. Effect of a vitamin-A-deficient diet, J. Nutr. Biochem., 24, 859, 10.1016/j.jnutbio.2012.05.006 Nelson, 2009, Alzheimer's-type neuropathology in the precuneus is not increased relative to other areas of neocortex across a range of cognitive impairment, Neurosci. Lett., 450, 336, 10.1016/j.neulet.2008.11.006 O'Byrne, 2013, Retinol and retinyl esters: biochemistry and physiology, J. Lipid Res., 54, 1731, 10.1194/jlr.R037648 Olson, 2010, Significance of vitamin A to brain function, behavior and learning, Mol. Nutr. Food Res., 54, 489, 10.1002/mnfr.200900246 Ono, 2012, Vitamin A and Alzheimer's disease, Geriatr Gerontol Int, 12, 180, 10.1111/j.1447-0594.2011.00786.x Pfaffl, 2001, A new mathematical model for relative quantification in real-time RT-PCR, Nucleic Acids Res., 29, e45, 10.1093/nar/29.9.e45 Ransom, 2014, The rhythm of retinoids in the brain, J. Neurochem., 129, 366, 10.1111/jnc.12620 Rinaldi, 2003, Plasma antioxidants are similarly depleted in mild cognitive impairment and in Alzheimer's disease, Neurobiol. Aging, 24, 915, 10.1016/S0197-4580(03)00031-9 Saari, 2016, Vitamin A and vision, Subcell. Biochem., 81, 231, 10.1007/978-94-024-0945-1_9 Sárvári, 2015, Hippocampal gene expression is highly responsive to estradiol replacement in middle-aged female rats, Endocrinology, 156, 2632, 10.1210/en.2015-1109 Scheltens, 2016, Alzheimer's disease, Lancet, 388, 505, 10.1016/S0140-6736(15)01124-1 Scheyer, 2018, Female sex and Alzheimer's risk: the menopause connection, J. Prev. Alzheimers Dis., 5, 225 Seleiro, 1994, The chicken retinoid-X-receptor-gamma gene gives rise to two distinct species of mRNA with different patterns of expression, Biochem. J., 301, 283, 10.1042/bj3010283 Shearer, 2012, A vitamin for the brain, Trends Neurosci., 35, 733, 10.1016/j.tins.2012.08.005 Silva, 2019, Alzheimer’s disease: risk factors and potentially protective measures, J. Biomed. Sci., 26, 33, 10.1186/s12929-019-0524-y Skaper, 2012, Alzheimer’s disease and amyloid: culprit or coincidence?, Int. Rev. Neurobiol., 102, 277, 10.1016/B978-0-12-386986-9.00011-9 Sodhi, 2014, Retinoids as potential targets for Alzheimer's disease, Pharmacol. Biochem. Behav., 120, 117, 10.1016/j.pbb.2014.02.016 Sołtys, 2020, Ordered structure-forming properties of the intrinsically disordered AB region of hRXRγ and its ability to promote liquid-liquid phase separation, J. Steroid Biochem. Mol. Biol., 198, 105571, 10.1016/j.jsbmb.2019.105571 St-Amour, 2014, IVIg protects the 3xTg-AD mouse model of Alzheimer’s disease from memory deficit and Abeta pathology, J. Neuroinflammation, 11, 54, 10.1186/1742-2094-11-54 Stoney, 2016, A vitamin on the mind: new discoveries on control of the brain by vitamin A, World Rev. Nutr. Diet., 115, 98, 10.1159/000442076 Succari, 1991, Influence of sex and age on vitamin A and E status, Age Ageing, 20, 413, 10.1093/ageing/20.6.413 Tanumihardjo, 2014, Usefulness of vitamin A isotope methods for status assessment: from deficiency through excess, Int. J. Vitam. Nutr. Res., 84, 16, 10.1024/0300-9831/a000182 Thal, 2002, Phases of A beta-deposition in the human brain and its relevance for the development of AD, Neurology, 58, 1791, 10.1212/WNL.58.12.1791 Tippmann, 2009, Up-regulation of the alpha-secretase ADAM10 by retinoic acid receptors and acitretin, FASEB J., 23, 1643, 10.1096/fj.08-121392 Tournissac, 2019, Repeated cold exposures protect a mouse model of Alzheimer's disease against cold-induced Tau phosphorylation, Mol. Metab., 22, 110, 10.1016/j.molmet.2019.01.008 Tousi, 2015, The emerging role of bexarotene in the treatment of Alzheimer’s disease: current evidence, Neuropsychiatr. Dis. Treat., 11, 311, 10.2147/NDT.S61309 Touyarot, 2013, A mid-life vitamin A supplementation prevents age-related spatial memory deficits and hippocampal neurogenesis alterations through CRABP-I, PLoS One, 8, 10.1371/journal.pone.0072101 Tremblay, 2007, Biochemical characterization of Abeta and Tau pathologies in mild cognitive impairment and Alzheimer’s disease, J. Alzheimers Dis., 12, 377, 10.3233/JAD-2007-12411 Tremblay, 2017, Association of neuropathological markers in the parietal cortex with antemortem cognitive function in persons with mild cognitive impairment and Alzheimer disease, J. Neuropathol. Exp. Neurol., 275, 204 Tromp, 2015, Episodic memory in normal aging and Alzheimer disease: insights from imaging and behavioral studies, Ageing Res. Rev., 24, 232, 10.1016/j.arr.2015.08.006 Vandal, 2015, Age-dependent impairment of glucose tolerance in the 3xTg-AD mouse model of Alzheimer's disease, FASEB J., 29, 4273, 10.1096/fj.14-268482 Wahl, 2017, Cognitive and behavioral evaluation of nutritional interventions in rodent models of brain aging and dementia, Clin. Interv. Aging, 12, 1419, 10.2147/CIA.S145247 Wang, 2015, All-trans-retinoic acid reduces BACE1 expression under inflammatory conditions via modulation of nuclear factor κB (NFκB) signaling, J. Biol. Chem., 290, 22532, 10.1074/jbc.M115.662908 Watamura, 2016, Colocalization of phosphorylated forms of WAVE1, CRMP2, and Tau in Alzheimer's disease model mice: involvement of Cdk5 phosphorylation and the effect of ATRA treatment, J. Neurosci. Res., 94, 15, 10.1002/jnr.23674 Wilson, 2002, Individual differences in rates of change in cognitive abilities of older persons, Psychol. Aging, 17, 179, 10.1037/0882-7974.17.2.179 Winblad, 2016, Defeating Alzheimer’s disease and other dementias: a priority for European science and society, Lancet Neurol., 15, 455, 10.1016/S1474-4422(16)00062-4 Yamagata, 2015, Retinoic acid has the potential to suppress endometriosis development, Journal of Ovarian Research, 8, 10.1186/s13048-015-0179-6 Yang, 2017, Effects of electroacupuncture and the retinoid X receptor (RXR) signalling pathway on oligodendrocyte differentiation in the demyelinated spinal cord of rats, Acupunct. Med., 35, 122, 10.1136/acupmed-2016-011134 Yang, 2018, Sex differences in neuropathology and cognitive behavior in APP/PS1/Tau triple-transgenic mouse model of Alzheimer’s disease, Neurosci. Bull., 34, 736, 10.1007/s12264-018-0268-9 Yilmaz, 2019, Endometriosis and nuclear receptors, Hum Reprod Update, 25, 473, 10.1093/humupd/dmz005 You, 2009, Retinoid X receptor-alpha mediates (R)-flurbiprofen's effect on the levels of Alzheimer's beta-amyloid, J. Neurochem., 111, 142, 10.1111/j.1471-4159.2009.06312.x Zanco, 2018, Spatial navigation in the elderly with Alzheimer's disease: a cross-sectional study, J. Alzheimers Dis., 66, 1683, 10.3233/JAD-180819 Zeng, 2017, Marginal vitamin A deficiency facilitates Alzheimer's pathogenesis, Acta Neuropathol., 133, 967, 10.1007/s00401-017-1669-y