Abstract
The choroid plexus comprises of a monolayer of tightly connected epithelial cells that form an important physical, enzymatic, and immunologic barrier, called the blood–cerebrospinal fluid (CSF) barrier. It is a highly vascularized structure located in the brain ventricles and plays a key role in maintaining brain homeostasis by producing CSF.
During aging, the morphology and normal function of the choroid plexus is compromised. Different alterations of the choroid plexus have been reported such as atrophy of the choroid plexus epithelial cells, decreased CSF production and secretion, decreased CSF clearance and absorption resulting in reduced clearance of toxic compounds, reduced enzymatic and metabolic activity, loss of barrier integrity, and insufficient distribution of nutrients. The described degeneration of the structure and function of the choroid plexus can result in multiple brain deficits and contribute to cognitive deterioration. In fact, these alterations of the choroid plexus are even more prominent in age-related neurodegenerative diseases including late-onset Alzheimer’s disease. A better understanding of the alterations in structure, activity, and function of the choroid plexus epithelial cells during aging and how the choroid plexus is implicated in aging and age-associated neurological diseases might reveal novel strategies to combat age-related cognitive decline and age-related neurological disorders.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Albeck MJ, Skak C, Nielsen PR, Olsen KS, Borgesen SE, Gjerris F (1998) Age dependency of resistance to cerebrospinal fluid outflow. J Neurosurg 89:275–278
Arking DE, Krebsova A, Macek M Sr, Macek M Jr, Arking A, Mian IS, Fried L, Hamosh A, Dey S, Mcintosh I, Dietz HC (2002) Association of human aging with a functional variant of klotho. Proc Natl Acad Sci U S A 99:856–861
Arking DE, Becker DM, Yanek LR, Fallin D, Judge DP, Moy TF, Becker LC, Dietz HC (2003) KLOTHO allele status and the risk of early-onset occult coronary artery disease. Am J Hum Genet 72:1154–1161
Arking DE, Atzmon G, Arking A, Barzilai N, Dietz HC (2005) Association between a functional variant of the KLOTHO gene and high-density lipoprotein cholesterol, blood pressure, stroke, and longevity. Circ Res 96:412–418
Baird GS, Nelson SK, Keeney TR, Stewart A, Williams S, Kraemer S, Peskind ER, Montine TJ (2012) Age-dependent changes in the cerebrospinal fluid proteome by slow off-rate modified aptamer array. Am J Pathol 180:446–456
Baixauli F, Lopez-Otin C, Mittelbrunn M (2014) Exosomes and autophagy: coordinated mechanisms for the maintenance of cellular fitness. Front Immunol 5:403
Balusu S, Brkic M, Libert C, Vandenbroucke RE (2016a) The choroid plexus-cerebrospinal fluid interface in Alzheimer’s disease: more than just a barrier. Neural Regen Res 11:534–537
Balusu S, Van Wonterghem E, De Rycke R, Raemdonck K, Stremersch S, Gevaert K, Brkic M, Demeestere D, Vanhooren V, Hendrix A, Libert C, Vandenbroucke RE (2016b) Identification of a novel mechanism of blood-brain communication during peripheral inflammation via choroid plexus-derived extracellular vesicles. EMBO Mol Med 8:1162–1183
Barkhof F, Kouwenhoven M, Scheltens P, Sprenger M, Algra P, Valk J (1994) Phase-contrast cine MR imaging of normal aqueductal CSF flow. Effect of aging and relation to CSF void on modulus MR. Acta Radiol 35:123–130
Bartke A, Sun LY, Longo V (2013) Somatotropic signaling: trade-offs between growth, reproductive development, and longevity. Physiol Rev 93:571–598
Baruch K, Ron-Harel N, Gal H, Deczkowska A, Shifrut E, Ndifon W, Mirlas-Neisberg N, Cardon M, Vaknin I, Cahalon L, Berkutzki T, Mattson MP, Gomez-Pinilla F, Friedman N, Schwartz M (2013) CNS-specific immunity at the choroid plexus shifts toward destructive Th2 inflammation in brain aging. Proc Natl Acad Sci U S A 110:2264–2269
Baruch K, Deczkowska A, David E, Castellano JM, Miller O, Kertser A, Berkutzki T, Barnett-Itzhaki Z, Bezalel D, Wyss-Coray T, Amit I, Schwartz M (2014) Aging. Aging-induced type I interferon response at the choroid plexus negatively affects brain function. Science 346:89–93
Baruch K, Kertser A, Porat Z, Schwartz M (2015) Cerebral nitric oxide represses choroid plexus NFkappaB-dependent gateway activity for leukocyte trafficking. EMBO J 34:1816–1828
Bellur SN, Chandra V, Mcdonald LW (1980) Arachnoidal cell hyperplasia. Its relationship to aging and chronic renal failure. Arch Pathol Lab Med 104:414–416
Blennow K, Fredman P, Wallin A, Gottfries CG, Karlsson I, Langstrom G, Skoog I, Svennerholm L, Wikkelso C (1993a) Protein analysis in cerebrospinal fluid. II. Reference values derived from healthy individuals 18–88 years of age. Eur Neurol 33:129–133
Blennow K, Fredman P, Wallin A, Gottfries CG, Langstrom G, Svennerholm L (1993b) Protein analyses in cerebrospinal fluid. I. Influence of concentration gradients for proteins on cerebrospinal fluid/serum albumin ratio. Eur Neurol 33:126–128
Blennow K, Fredman P, Wallin A, Gottfries CG, Skoog I, Wikkelso C, Svennerholm L (1993c) Protein analysis in cerebrospinal fluid. III. Relation to blood-cerebrospinal fluid barrier function for formulas for quantitative determination of intrathecal IgG production. Eur Neurol 33:134–142
Bolos M, Antequera D, Aldudo J, Kristen H, Bullido MJ, Carro E (2014) Choroid plexus implants rescue Alzheimer’s disease-like pathologies by modulating amyloid-beta degradation. Cell Mol Life Sci 71:2947–2955
Borlongan CV, Skinner SJ, Geaney M, Vasconcellos AV, Elliott RB, Emerich DF (2004a) CNS grafts of rat choroid plexus protect against cerebral ischemia in adult rats. Neuroreport 15:1543–1547
Borlongan CV, Skinner SJ, Geaney M, Vasconcellos AV, Elliott RB, Emerich DF (2004b) Intracerebral transplantation of porcine choroid plexus provides structural and functional neuroprotection in a rodent model of stroke. Stroke 35:2206–2210
Braak H, Braak E (1991) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 82:239–259
Brinker T, Stopa E, Morrison J, Klinge P (2014) A new look at cerebrospinal fluid circulation. Fluids Barriers CNS 11:10
Brkic M, Balusu S, Van Wonterghem E, Gorle N, Benilova I, Kremer A, Van Hove I, Moons L, De Strooper B, Kanazir S, Libert C, Vandenbroucke RE (2015) Amyloid beta oligomers disrupt blood-CSF barrier integrity by activating matrix metalloproteinases. J Neurosci 35:12766–12778
Brown PD, Davies SL, Speake T, Millar ID (2004) Molecular mechanisms of cerebrospinal fluid production. Neuroscience 129:957–970
Bulat M, Klarica M (2011) Recent insights into a new hydrodynamics of the cerebrospinal fluid. Brain Res Rev 65:99–112
Calder PC, Bosco N, Bourdet-Sicard R, Capuron L, Delzenne N, Dore J, Franceschi C, Lehtinen MJ, Recker T, Salvioli S, Visioli F (2017) Health relevance of the modification of low grade inflammation in ageing (inflammageing) and the role of nutrition. Ageing Res Rev 40:95–119
Chen J, Buchanan JB, Sparkman NL, Godbout JP, Freund GG, Johnson RW (2008) Neuroinflammation and disruption in working memory in aged mice after acute stimulation of the peripheral innate immune system. Brain Behav Immun 22:301–311
Chen RL, Kassem NA, Redzic ZB, Chen CP, Segal MB, Preston JE (2009) Age-related changes in choroid plexus and blood-cerebrospinal fluid barrier function in the sheep. Exp Gerontol 44:289–296
Chen CP, Chen RL, Preston JE (2012a) The influence of ageing in the cerebrospinal fluid concentrations of proteins that are derived from the choroid plexus, brain, and plasma. Exp Gerontol 47:323–328
Chen X, Guo C, Kong J (2012b) Oxidative stress in neurodegenerative diseases. Neural Regen Res 7:376–385
Chen CD, Sloane JA, Li H, Aytan N, Giannaris EL, Zeldich E, Hinman JD, Dedeoglu A, Rosene DL, Bansal R, Luebke JI, Kuro OM, Abraham CR (2013) The antiaging protein Klotho enhances oligodendrocyte maturation and myelination of the CNS. J Neurosci 33:1927–1939
Chen CPC, Preston JE, Zhou S, Fuller HR, Morgan DGA, Chen R (2018) Proteomic analysis of age-related changes in ovine cerebrospinal fluid. Exp Gerontol 108:181–188
Chiu C, Miller MC, Caralopoulos IN, Worden MS, Brinker T, Gordon ZN, Johanson CE, Silverberg GD (2012) Temporal course of cerebrospinal fluid dynamics and amyloid accumulation in the aging rat brain from three to thirty months. Fluids Barriers CNS 9:3
Chodobski A, Szmydynger-Chodobska J (2001) Choroid plexus: target for polypeptides and site of their synthesis. Microsc Res Tech 52:65–82
Chongbin L, Rui W, Chunyan W, Hu C, Qifeng D (2014) Altered hepcidin expression is part of the choroid plexus response to IL-6/Stat3 signaling pathway in normal aging rats. Bioenergetics 3:2
Christensen HL, Barbuskaite D, Rojek A, Malte H, Christensen IB, Fuchtbauer AC, Fuchtbauer EM, Wang T, Praetorius J, Damkier HH (2018) The choroid plexus sodium-bicarbonate cotransporter NBCe2 regulates mouse cerebrospinal fluid pH. J Physiol 596:4709–4728
Cohen P, Ocrant I, Fielder PJ, Neely EK, Gargosky SE, Deal CI, Ceda GP, Youngman O, Pham H, Lamson G et al (1992) Insulin-like growth factors (IGFs): implications for aging. Psychoneuroendocrinology 17:335–342
Cornford EM, Varesi JB, Hyman S, Damian RT, Raleigh MJ (1997) Mitochondrial content of choroid plexus epithelium. Exp Brain Res 116:399–405
Cottrell DA, Blakely EL, Johnson MA, Ince PG, Borthwick GM, Turnbull DM (2001) Cytochrome c oxidase deficient cells accumulate in the hippocampus and choroid plexus with age. Neurobiol Aging 22:265–272
Cutler RW, Page L, Galicich J, Watters GV (1968) Formation and absorption of cerebrospinal fluid in man. Brain 91:707–720
Damkier HH, Brown PD, Praetorius J (2013) Cerebrospinal fluid secretion by the choroid plexus. Physiol Rev 93:1847–1892
Daouk J, Bouzerar R, Chaarani B, Zmudka J, Meyer ME, Baledent O (2016) Use of dynamic (18) F-fluorodeoxyglucose positron emission tomography to investigate choroid plexus function in Alzheimer’s disease. Exp Gerontol 77:62–68
De Bock M, Vandenbroucke RE, Decrock E, Culot M, Cecchelli R, Leybaert L (2014) A new angle on blood-CNS interfaces: a role for connexins? FEBS Lett 588:1259–1270
Deane R, Zheng W, Zlokovic BV (2004) Brain capillary endothelium and choroid plexus epithelium regulate transport of transferrin-bound and free iron into the rat brain. J Neurochem 88:813–820
Deczkowska A, Baruch K, Schwartz M (2016) Type I/II interferon balance in the regulation of brain physiology and pathology. Trends Immunol 37:181–192
Demeestere D, Libert C, Vandenbroucke RE (2015) Clinical implications of leukocyte infiltration at the choroid plexus in (neuro)inflammatory disorders. Drug Discov Today 20:928–941
Duce JA, Podvin S, Hollander W, Kipling D, Rosene DL, Abraham CR (2008) Gene profile analysis implicates Klotho as an important contributor to aging changes in brain white matter of the rhesus monkey. Glia 56:106–117
Emerich DF, Borlongan CV (2009) Potential of choroid plexus epithelial cell grafts for neuroprotection in Huntington’s disease: what remains before considering clinical trials. Neurotox Res 15:205–211
Emerich DF, Skinner SJ, Borlongan CV, Vasconcellos AV, Thanos CG (2005) The choroid plexus in the rise, fall and repair of the brain. BioEssays 27:262–274
Emerich DF, Schneider P, Bintz B, Hudak J, Thanos CG (2007) Aging reduces the neuroprotective capacity, VEGF secretion, and metabolic activity of rat choroid plexus epithelial cells. Cell Transplant 16:697–705
Endo H, Sasaki K, Tonosaki A, Kayama T (1998) Three-dimensional and ultrastructural ICAM-1 distribution in the choroid plexus, arachnoid membrane and dural sinus of inflammatory rats induced by LPS injection in the lateral ventricles. Brain Res 793:297–301
Engelhardt B, Coisne C (2011) Fluids and barriers of the CNS establish immune privilege by confining immune surveillance to a two-walled castle moat surrounding the CNS castle. Fluids Barriers CNS 8:4
Engelhardt B, Ransohoff RM (2012) Capture, crawl, cross: the T cell code to breach the blood-brain barriers. Trends Immunol 33:579–589
Eriksson L, Westermark P (1986) Intracellular neurofibrillary tangle-like aggregations. A constantly present amyloid alteration in the aging choroid plexus. Am J Pathol 125:124–129
Falcao AM, Marques F, Novais A, Sousa N, Palha JA, Sousa JC (2012) The path from the choroid plexus to the subventricular zone: go with the flow! Front Cell Neurosci 6:34
Faraci FM, Mayhan WG, Farrell WJ, Heistad DD (1988) Humoral regulation of blood flow to choroid plexus: role of arginine vasopressin. Circ Res 63:373–379
Faubel R, Westendorf C, Bodenschatz E, Eichele G (2016) Cilia-based flow network in the brain ventricles. Science 353:176–178
Ferrante F, Amenta F (1987) Enzyme histochemistry of the choroid plexus in old rats. Mech Ageing Dev 41:65–72
Fleischman D, Berdahl JP, Zaydlarova J, Stinnett S, Fautsch MP, Allingham RR (2012) Cerebrospinal fluid pressure decreases with older age. PLoS One 7:e52664
Foundas AL, Zipin D, Browning CA (1998) Age-related changes of the insular cortex and lateral ventricles: conventional MRI volumetric measures. J Neuroimaging 8:216–221
Franceschi C (2007) Inflammaging as a major characteristic of old people: can it be prevented or cured? Nutr Rev 65:S173–S176
Franceschi C, Campisi J (2014) Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J Gerontol A Biol Sci Med Sci 69(Suppl 1):S4–S9
Frolkis VV, Kvitnitskaya-Ryzhova TY, Dubiley TA (1999) Vasopressin, hypothalamo-neurohypophyseal system and aging. Arch Gerontol Geriatr 29:193–214
Galea I, Bechmann I, Perry VH (2007) What is immune privilege (not)? Trends Immunol 28:12–18
Garner CC, Waites CL, Ziv NE (2006) Synapse development: still looking for the forest, still lost in the trees. Cell Tissue Res 326:249–262
Garton MJ, Keir G, Lakshmi MV, Thompson EJ (1991) Age-related changes in cerebrospinal fluid protein concentrations. J Neurol Sci 104:74–80
Gideon P, Thomsen C, Stahlberg F, Henriksen O (1994) Cerebrospinal fluid production and dynamics in normal aging: a MRI phase-mapping study. Acta Neurol Scand 89:362–366
Gorle N, Van Cauwenberghe C, Libert C, Vandenbroucke RE (2016) The effect of aging on brain barriers and the consequences for Alzheimer’s disease development. Mamm Genome 27:407–420
Grapp M, Wrede A, Schweizer M, Huwel S, Galla HJ, Snaidero N, Simons M, Buckers J, Low PS, Urlaub H, Gartner J, Steinfeld R (2013) Choroid plexus transcytosis and exosome shuttling deliver folate into brain parenchyma. Nat Commun 4:2123
Henriksson L, Voigt K (1976) Age-dependent differences of distribution and clearance patterns in normal RIHSA cisternograms. Neuroradiology 12:103–107
Henry CJ, Huang Y, Wynne AM, Godbout JP (2009) Peripheral lipopolysaccharide (LPS) challenge promotes microglial hyperactivity in aged mice that is associated with exaggerated induction of both pro-inflammatory IL-1beta and anti-inflammatory IL-10 cytokines. Brain Behav Immun 23:309–317
Holm NR, Hansen LB, Nilsson C, Gammeltoft S (1994) Gene expression and secretion of insulin-like growth factor-II and insulin-like growth factor binding protein-2 from cultured sheep choroid plexus epithelial cells. Brain Res Mol Brain Res 21:67–74
Hubert V, Chauveau F, Dumot C, Ong E, Berner LP, Canet-Soulas E, Ghersi-Egea JF, Wiart M (2019) Clinical imaging of choroid plexus in health and in brain disorders: a mini-review. Front Mol Neurosci 12:34
Imura A, Iwano A, Tohyama O, Tsuji Y, Nozaki K, Hashimoto N, Fujimori T, Nabeshima Y (2004) Secreted Klotho protein in sera and CSF: implication for post-translational cleavage in release of Klotho protein from cell membrane. FEBS Lett 565:143–147
Jahng GH, Oh J, Lee DW, Kim HG, Rhee HY, Shin W, Paik JW, Lee KM, Park S, Choe BY, Ryu CW (2016) Glutamine and glutamate complex, as measured by functional magnetic resonance spectroscopy, alters during face-name association task in patients with mild cognitive impairment and Alzheimer’s disease. J Alzheimers Dis 52:145–159
Jellinger K (1976) Neuropathological aspects of dementias resulting from abnormal blood and cerebrospinal fluid dynamics. Acta Neurol Belg 76:83–102
Johanson CE, Duncan JA 3rd, Klinge PM, Brinker T, Stopa EG, Silverberg GD (2008) Multiplicity of cerebrospinal fluid functions: new challenges in health and disease. Cerebrospinal Fluid Res 5:10
Jost BC, Grossberg GT (1995) The natural history of Alzheimer’s disease: a brain bank study. J Am Geriatr Soc 43:1248–1255
Jovanovic I, Stefanovic N, Antic S, Ugrenovic S, Djindjic B, Vidovic N (2004) Morphological and morphometric characteristics of choroid plexus psammoma bodies during the human aging. Ital J Anat Embryol 109:19–33
Kao L, Kurtz LM, Shao X, Papadopoulos MC, Liu L, Bok D, Nusinowitz S, Chen B, Stella SL, Andre M, Weinreb J, Luong SS, Piri N, Kwong JM, Newman D, Kurtz I (2011) Severe neurologic impairment in mice with targeted disruption of the electrogenic sodium bicarbonate cotransporter NBCe2 (Slc4a5 gene). J Biol Chem 286:32563–32574
Kaur C, Rathnasamy G, Ling EA (2016) The choroid plexus in healthy and diseased brain. J Neuropathol Exp Neurol 75:198–213
Khasawneh AH, Garling RJ, Harris CA (2018) Cerebrospinal fluid circulation: what do we know and how do we know it? Brain Circ 4:14–18
Kida S, Yamashima T, Kubota T, Ito H, Yamamoto S (1988) A light and electron microscopic and immunohistochemical study of human arachnoid villi. J Neurosurg 69:429–435
Kleine TO, Hackler R, Lutcke A, Dauch W, Zofel P (1993a) Transport and production of cerebrospinal fluid (CSF) change in aging humans under normal and diseased conditions. Z Gerontol 26:251–255
Kleine TO, Hackler R, Zofel P (1993b) Age-related alterations of the blood-brain-barrier (bbb) permeability to protein molecules of different size. Z Gerontol 26:256–259
Kunis G, Baruch K, Rosenzweig N, Kertser A, Miller O, Berkutzki T, Schwartz M (2013) IFN-gamma-dependent activation of the brain’s choroid plexus for CNS immune surveillance and repair. Brain 136:3427–3440
Kuro OM (2010) Klotho. Pflugers Arch 459:333–343
Kuro OM, Matsumura Y, Aizawa H, Kawaguchi H, Suga T, Utsugi T, Ohyama Y, Kurabayashi M, Kaname T, Kume E, Iwasaki H, Iida A, Shiraki-Iida T, Nishikawa S, Nagai R, Nabeshima YI (1997) Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature 390:45–51
Kurosu H, Yamamoto M, Clark JD, Pastor JV, Nandi A, Gurnani P, Mcguinness OP, Chikuda H, Yamaguchi M, Kawaguchi H, Shimomura I, Takayama Y, Herz J, Kahn CR, Rosenblatt KP, Kuro OM (2005) Suppression of aging in mice by the hormone Klotho. Science 309:1829–1833
Kvitnitskaia-Ryzhova T, Shkapenko AL (1992) A comparative ultracytochemical and biochemical study of the ATPases of the choroid plexus in aging. Tsitologiia 34:81–87
Leitner DF, Connor JR (2012) Functional roles of transferrin in the brain. Biochim Biophys Acta 1820:393–402
Lenoir D, Honegger P (1983) Insulin-like growth factor I (IGF I) stimulates DNA synthesis in fetal rat brain cell cultures. Brain Res 283:205–213
Li D, Jing D, Liu Z, Chen Y, Huang F, Behnisch T (2019) Enhanced expression of secreted alpha-klotho in the hippocampus alters nesting behavior and memory formation in mice. Front Cell Neurosci 13:133
Liddelow SA (2015) Development of the choroid plexus and blood-CSF barrier. Front Neurosci 9:32
Lindsey AE, Schneider K, Simmons DM, Baron R, Lee BS, Kopito RR (1990) Functional expression and subcellular localization of an anion exchanger cloned from choroid plexus. Proc Natl Acad Sci U S A 87:5278–5282
Lu J, Kaur C, Ling EA (1995) Expression and upregulation of transferrin receptors and iron uptake in the epiplexus cells of different aged rats injected with lipopolysaccharide and interferon-gamma. J Anat 187(Pt 3):603–611
Lun MP, Johnson MB, Broadbelt KG, Watanabe M, Kang YJ, Chau KF, Springel MW, Malesz A, Sousa AM, Pletikos M, Adelita T, Calicchio ML, Zhang Y, Holtzman MJ, Lidov HG, Sestan N, Steen H, Monuki ES, Lehtinen MK (2015) Spatially heterogeneous choroid plexus transcriptomes encode positional identity and contribute to regional CSF production. J Neurosci 35:4903–4916
Ma Q, Ineichen BV, Detmar M, Proulx ST (2017) Outflow of cerebrospinal fluid is predominantly through lymphatic vessels and is reduced in aged mice. Nat Commun 8:1434
Main BS, Zhang M, Brody KM, Kirby FJ, Crack PJ, Taylor JM (2017) Type-I interferons mediate the neuroinflammatory response and neurotoxicity induced by rotenone. J Neurochem 141:75–85
Manouchehrinia A, Constantinescu CS (2012) Cost-effectiveness of disease-modifying therapies in multiple sclerosis. Curr Neurol Neurosci Rep 12:592–600
Marques F, Sousa JC (2015) The choroid plexus is modulated by various peripheral stimuli: implications to diseases of the central nervous system. Front Cell Neurosci 9:136
Marques F, Sousa JC, Correia-Neves M, Oliveira P, Sousa N, Palha JA (2007) The choroid plexus response to peripheral inflammatory stimulus. Neuroscience 144:424–430
Marques F, Falcao AM, Sousa JC, Coppola G, Geschwind D, Sousa N, Correia-Neves M, Palha JA (2009) Altered iron metabolism is part of the choroid plexus response to peripheral inflammation. Endocrinology 150:2822–2828
Marques F, Sousa JC, Coppola G, Gao F, Puga R, Brentani H, Geschwind DH, Sousa N, Correia-Neves M, Palha JA (2011) Transcriptome signature of the adult mouse choroid plexus. Fluids Barriers CNS 8:10
Marques F, Sousa JC, Sousa N, Palha JA (2013) Blood-brain-barriers in aging and in Alzheimer’s disease. Mol Neurodegener 8:38
Marques F, Sousa JC, Brito MA, Pahnke J, Santos C, Correia-Neves M, Palha JA (2017) The choroid plexus in health and in disease: dialogues into and out of the brain. Neurobiol Dis 107:32–40
Maslieieva V, Thompson RJ (2014) A critical role for pannexin-1 in activation of innate immune cells of the choroid plexus. Channels (Austin) 8:131–141
Masseguin C, Lepanse S, Corman B, Verbavatz JM, Gabrion J (2005) Aging affects choroidal proteins involved in CSF production in Sprague-Dawley rats. Neurobiol Aging 26:917–927
Mathieu M, Martin-Jaular L, Lavieu G, Thery C (2019) Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication. Nat Cell Biol 21:9–17
Matsumae M, Kikinis R, Morocz I, Lorenzo AV, Albert MS, Black PM, Jolesz FA (1996a) Intracranial compartment volumes in patients with enlarged ventricles assessed by magnetic resonance-based image processing. J Neurosurg 84:972–981
Matsumae M, Kikinis R, Morocz IA, Lorenzo AV, Sandor T, Albert MS, Black PM, Jolesz FA (1996b) Age-related changes in intracranial compartment volumes in normal adults assessed by magnetic resonance imaging. J Neurosurg 84:982–991
May C, Kaye JA, Atack JR, Schapiro MB, Friedland RP, Rapoport SI (1990) Cerebrospinal fluid production is reduced in healthy aging. Neurology 40:500–503
Mergenthaler P, Lindauer U, Dienel GA, Meisel A (2013) Sugar for the brain: the role of glucose in physiological and pathological brain function. Trends Neurosci 36:587–597
Miklossy J, Kraftsik R, Pillevuit O, Lepori D, Genton C, Bosman FT (1998) Curly fiber and tangle-like inclusions in the ependyma and choroid plexus--a pathogenetic relationship with the cortical Alzheimer-type changes? J Neuropathol Exp Neurol 57:1202–1212
Mill JF, Chao MV, Ishii DN (1985) Insulin, insulin-like growth factor II, and nerve growth factor effects on tubulin mRNA levels and neurite formation. Proc Natl Acad Sci U S A 82:7126–7130
Mittelbrunn M, Sanchez-Madrid F (2012) Intercellular communication: diverse structures for exchange of genetic information. Nat Rev Mol Cell Biol 13:328–335
Morris CM, Keith AB, Edwardson JA, Pullen RG (1992) Uptake and distribution of iron and transferrin in the adult rat brain. J Neurochem 59:300–306
Mozell RL, Mcmorris FA (1991) Insulin-like growth factor I stimulates oligodendrocyte development and myelination in rat brain aggregate cultures. J Neurosci Res 30:382–390
Nilsson C, Lindvall-Axelsson M, Owman C (1992) Neuroendocrine regulatory mechanisms in the choroid plexus-cerebrospinal fluid system. Brain Res Brain Res Rev 17:109–138
Nilsson C, Hultberg BM, Gammeltoft S (1996) Autocrine role of insulin-like growth factor II secretion by the rat choroid plexus. Eur J Neurosci 8:629–635
Ogata N, Matsumura Y, Shiraki M, Kawano K, Koshizuka Y, Hosoi T, Nakamura K, Kuro OM, Kawaguchi H (2002) Association of klotho gene polymorphism with bone density and spondylosis of the lumbar spine in postmenopausal women. Bone 31:37–42
Paolicelli RC, Bergamini G, Rajendran L (2018) Cell-to-cell communication by extracellular vesicles: focus on microglia. Neuroscience 405:148–157
Pascale CL, Miller MC, Chiu C, Boylan M, Caralopoulos IN, Gonzalez L, Johanson CE, Silverberg GD (2011) Amyloid-beta transporter expression at the blood-CSF barrier is age-dependent. Fluids Barriers CNS 8:21
Pershing LK, Johanson CE (1982) Acidosis-induced enhanced activity of the Na-K exchange pump in the in vivo choroid plexus: an ontogenetic analysis of possible role in cerebrospinal fluid pH homeostasis. J Neurochem 38:322–332
Phillipson M, Kaur J, Colarusso P, Ballantyne CM, Kubes P (2008) Endothelial domes encapsulate adherent neutrophils and minimize increases in vascular permeability in paracellular and transcellular emigration. PLoS One 3:e1649
Plotkin MD, Kaplan MR, Peterson LN, Gullans SR, Hebert SC, Delpire E (1997) Expression of the Na(+)-K(+)-2Cl- cotransporter BSC2 in the nervous system. Am J Phys 272:C173–C183
Preston JE (2001) Ageing choroid plexus-cerebrospinal fluid system. Microsc Res Tech 52:31–37
Proulx ST, Ma Q, Andina D, Leroux JC, Detmar M (2017) Quantitative measurement of lymphatic function in mice by noninvasive near-infrared imaging of a peripheral vein. JCI Insight 2:e90861
Ransohoff RM, Engelhardt B (2012) The anatomical and cellular basis of immune surveillance in the central nervous system. Nat Rev Immunol 12:623–635
Redzic Z (2011) Molecular biology of the blood-brain and the blood-cerebrospinal fluid barriers: similarities and differences. Fluids Barriers CNS 8:3
Redzic ZB, Segal MB (2004) The structure of the choroid plexus and the physiology of the choroid plexus epithelium. Adv Drug Deliv Rev 56:1695–1716
Redzic ZB, Preston JE, Duncan JA, Chodobski A, Szmydynger-Chodobska J (2005) The choroid plexus-cerebrospinal fluid system: from development to aging. Curr Top Dev Biol 71:1–52
Report WA (2018) World Alzheimer report
Rouault TA, Zhang DL, Jeong SY (2009) Brain iron homeostasis, the choroid plexus, and localization of iron transport proteins. Metab Brain Dis 24:673–684
Rubenstein E (1998) Relationship of senescence of cerebrospinal fluid circulatory system to dementias of the aged. Lancet 351:283–285
Sakka L, Coll G, Chazal J (2011) Anatomy and physiology of cerebrospinal fluid. Eur Ann Otorhinolaryngol Head Neck Dis 128:309–316
Sathyanesan M, Girgenti MJ, Banasr M, Stone K, Bruce C, Guilchicek E, Wilczak-Havill K, Nairn A, Williams K, Sass S, Duman JG, Newton SS (2012) A molecular characterization of the choroid plexus and stress-induced gene regulation. Transl Psychiatry 2:e139
Saunders NR, Daneman R, Dziegielewska KM, Liddelow SA (2013) Transporters of the blood-brain and blood-CSF interfaces in development and in the adult. Mol Asp Med 34:742–752
Schwarzman AL, Gregori L, Vitek MP, Lyubski S, Strittmatter WJ, Enghilde JJ, Bhasin R, Silverman J, Weisgraber KH, Coyle PK et al (1994) Transthyretin sequesters amyloid beta protein and prevents amyloid formation. Proc Natl Acad Sci U S A 91:8368–8372
Segal MB (2000) The choroid plexuses and the barriers between the blood and the cerebrospinal fluid. Cell Mol Neurobiol 20:183–196
Semba RD, Moghekar AR, Hu J, Sun K, Turner R, Ferrucci L, O’Brien R (2014) Klotho in the cerebrospinal fluid of adults with and without Alzheimer’s disease. Neurosci Lett 558:37–40
Serot JM, Christmann D, Dubost T, Couturier M (1997) Cerebrospinal fluid transthyretin: aging and late onset Alzheimer’s disease. J Neurol Neurosurg Psychiatry 63:506–508
Serot JM, Bene MC, Foliguet B, Faure GC (2000) Morphological alterations of the choroid plexus in late-onset Alzheimer’s disease. Acta Neuropathol 99:105–108
Serot JM, Foliguet B, Bene MC, Faure GC (2001) Choroid plexus and ageing in rats: a morphometric and ultrastructural study. Eur J Neurosci 14:794–798
Serot JM, Bene MC, Faure GC (2003) Choroid plexus, aging of the brain, and Alzheimer’s disease. Front Biosci 8:s515–s521
Shechter R, London A, Schwartz M (2013) Orchestrated leukocyte recruitment to immune-privileged sites: absolute barriers versus educational gates. Nat Rev Immunol 13:206–218
Shiozaki M, Yoshimura K, Shibata M, Koike M, Matsuura N, Uchiyama Y, Gotow T (2008) Morphological and biochemical signs of age-related neurodegenerative changes in klotho mutant mice. Neuroscience 152:924–941
Shuangshoti S, Netsky MG (1970) Human choroid plexus: morphologic and histochemical alterations with age. Am J Anat 128:73–95
Siesjo BK (1978) Brain metabolism and anaesthesia. Acta Anaesthesiol Scand Suppl 70:56–59
Silva-Vargas V, Maldonado-Soto AR, Mizrak D, Codega P, Doetsch F (2016) Age-dependent niche signals from the choroid plexus regulate adult neural stem cells. Cell Stem Cell 19:643–652
Silverberg GD, Heit G, Huhn S, Jaffe RA, Chang SD, Bronte-Stewart H, Rubenstein E, Possin K, Saul TA (2001) The cerebrospinal fluid production rate is reduced in dementia of the Alzheimer’s type. Neurology 57:1763–1766
Silverberg GD, Mayo M, Saul T, Rubenstein E, Mcguire D (2003) Alzheimer’s disease, normal-pressure hydrocephalus, and senescent changes in CSF circulatory physiology: a hypothesis. Lancet Neurol 2:506–511
Simpson IA, Carruthers A, Vannucci SJ (2007) Supply and demand in cerebral energy metabolism: the role of nutrient transporters. J Cereb Blood Flow Metab 27:1766–1791
Sparkman NL, Johnson RW (2008) Neuroinflammation associated with aging sensitizes the brain to the effects of infection or stress. Neuroimmunomodulation 15:323–330
Speake T, Whitwell C, Kajita H, Majid A, Brown PD (2001) Mechanisms of CSF secretion by the choroid plexus. Microsc Res Tech 52:49–59
Steinmann U, Borkowski J, Wolburg H, Schroppel B, Findeisen P, Weiss C, Ishikawa H, Schwerk C, Schroten H, Tenenbaum T (2013) Transmigration of polymorphnuclear neutrophils and monocytes through the human blood-cerebrospinal fluid barrier after bacterial infection in vitro. J Neuroinflammation 10:31
Stoquart-Elsankari S, Baledent O, Gondry-Jouet C, Makki M, Godefroy O, Meyer ME (2007) Aging effects on cerebral blood and cerebrospinal fluid flows. J Cereb Blood Flow Metab 27:1563–1572
Storck SE, Meister S, Nahrath J, Meissner JN, Schubert N, Di Spiezio A, Baches S, Vandenbroucke RE, Bouter Y, Prikulis I, Korth C, Weggen S, Heimann A, Schwaninger M, Bayer TA, Pietrzik CU (2016) Endothelial LRP1 transports amyloid-beta(1-42) across the blood-brain barrier. J Clin Invest 126:123–136
Strazielle N, Ghersi-Egea JF (2000) Choroid plexus in the central nervous system: biology and physiopathology. J Neuropathol Exp Neurol 59:561–574
Sturrock RR (1988) An ultrastructural study of the choroid plexus of aged mice. Anat Anz 165:379–385
Thanos CG, Bintz B, Emerich DF (2010) Microencapsulated choroid plexus epithelial cell transplants for repair of the brain. Adv Exp Med Biol 670:80–91
Thouvenot E, Lafon-Cazal M, Demettre E, Jouin P, Bockaert J, Marin P (2006) The proteomic analysis of mouse choroid plexus secretome reveals a high protein secretion capacity of choroidal epithelial cells. Proteomics 6:5941–5952
Tietje A, Maron KN, Wei Y, Feliciano DM (2014) Cerebrospinal fluid extracellular vesicles undergo age dependent declines and contain known and novel non-coding RNAs. PLoS One 9:e113116
Uchida A, Komiya Y, Tashiro T, Yorifuji H, Kishimoto T, Nabeshima Y, Hisanaga S (2001) Neurofilaments of Klotho, the mutant mouse prematurely displaying symptoms resembling human aging. J Neurosci Res 64:364–370
Van Niel G, D’Angelo G, Raposo G (2018) Shedding light on the cell biology of extracellular vesicles. Nat Rev Mol Cell Biol 19:213–228
Vandenbroucke RE (2016) A hidden epithelial barrier in the brain with a central role in regulating brain homeostasis. Implications for aging. Ann Am Thorac Soc 13(Suppl 5):S407–S410
Vandenbroucke RE, Dejonckheere E, Van Lint P, Demeestere D, Van Wonterghem E, Vanlaere I, Puimege L, Van Hauwermeiren F, De Rycke R, Mc Guire C, Campestre C, Lopez-Otin C, Matthys P, Leclercq G, Libert C (2012) Matrix metalloprotease 8-dependent extracellular matrix cleavage at the blood-CSF barrier contributes to lethality during systemic inflammatory diseases. J Neurosci 32:9805–9816
Vega JA, Del Valle ME, Calzada B, Bengoechea ME, Perez-Casas A (1992) Expression of nerve growth factor receptor immunoreactivity in the rat choroid plexus. Cell Mol Biol 38:145–149
Villeda SA, Luo J, Mosher KI, Zou B, Britschgi M, Bieri G, Stan TM, Fainberg N, Ding Z, Eggel A, Lucin KM, Czirr E, Park JS, Couillard-Despres S, Aigner L, Li G, Peskind ER, Kaye JA, Quinn JF, Galasko DR, Xie XS, Rando TA, Wyss-Coray T (2011) The ageing systemic milieu negatively regulates neurogenesis and cognitive function. Nature 477:90–94
Wahlund LO, Almkvist O, Basun H, Julin P (1996) MRI in successful aging, a 5-year follow-up study from the eighth to ninth decade of life. Magn Reson Imaging 14:601–608
Wen GY, Wisniewski HM, Kascsak RJ (1999) Biondi ring tangles in the choroid plexus of Alzheimer’s disease and normal aging brains: a quantitative study. Brain Res 832:40–46
Wewer C, Seibt A, Wolburg H, Greune L, Schmidt MA, Berger J, Galla HJ, Quitsch U, Schwerk C, Schroten H, Tenenbaum T (2011) Transcellular migration of neutrophil granulocytes through the blood-cerebrospinal fluid barrier after infection with Streptococcus suis. J Neuroinflammation 8:51
Wingerchuk DM, Carter JL (2014) Multiple sclerosis: current and emerging disease-modifying therapies and treatment strategies. Mayo Clin Proc 89:225–240
Wolburg H, Wolburg-Buchholz K, Engelhardt B (2005) Diapedesis of mononuclear cells across cerebral venules during experimental autoimmune encephalomyelitis leaves tight junctions intact. Acta Neuropathol 109:181–190
Yang Y, Keene CD, Peskind ER, Galasko DR, Hu SC, Cudaback E, Wilson AM, Li G, Yu CE, Montine KS, Zhang J, Baird GS, Hyman BT, Montine TJ (2015) Cerebrospinal fluid particles in Alzheimer disease and parkinson Disease. J Neuropathol Exp Neurol 74:672–687
Yesavage JA, Holman CA, Sarnquist FH, Berger PA (1982) Elevation of cerebrospinal fluid lactate with aging in subjects with normal blood oxygen saturations. J Gerontol 37:313–315
Zhu L, Stein LR, Kim D, Ho K, Yu GQ, Zhan L, Larsson TE, Mucke L (2018) Klotho controls the brain-immune system interface in the choroid plexus. Proc Natl Acad Sci U S A 115:E11388–E11396
Zivkovic VS, Stanojkovic MM, Antic MM (2017) Psammoma bodies as signs of choroid plexus ageing - a morphometric analysis. Vojnosanit Pregl 74:1054–1059
ZS-Nagy I, Steiber J, Jeney F (1995) Induction of age pigment accumulation in the brain cells of young male rats through iron-injection into the cerebrospinal fluid. Gerontology 41(Suppl 2):145–158
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2020 The American Physiological Society
About this chapter
Cite this chapter
Van Cauwenberghe, C., Gorlé, N., Vandenbroucke, R.E. (2020). Roles of the Choroid Plexus in Aging. In: Praetorius, J., Blazer-Yost, B., Damkier, H. (eds) Role of the Choroid Plexus in Health and Disease. Physiology in Health and Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-0716-0536-3_9
Download citation
DOI: https://doi.org/10.1007/978-1-0716-0536-3_9
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-0716-0535-6
Online ISBN: 978-1-0716-0536-3
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)