Peripheral inflammatory biomarkers in Alzheimer’s disease: a brief review
1
조회
0
다운로드
3
인용
0
참고문헌
키워드
초록
Alzheimer’s disease (AD) is a chronic neurodegenerative disease characterized by the accumulation of amyloid plaques and neurofibrillary tangles in the brain. The AD pathophysiology entails chronic inflammation involving innate immune cells including microglia, astrocytes, and other peripheral blood cells. Inflammatory mediators such as cytokines and complements are also linked to AD pathogenesis. Despite increasing evidence supporting the association between abnormal inflammation and AD, no well-established inflammatory biomarkers are currently available for AD. Since many reports have shown that abnormal inflammation precedes the outbreak of the disease, non-invasive and readily available peripheral inflammatory biomarkers should be considered as possible biomarkers for early diagnosis of AD. In this minireview, we introduce the peripheral biomarker candidates related to abnormal inflammation in AD and discuss their possible molecular mechanisms. Furthermore, we also summarize the current state of inflammatory biomarker research in clinical practice and molecular diagnostics. We believe this review will provide new insights into biomarker candidates for the early diagnosis of AD with systemic relevance to inflammation during AD pathogenesis.
Abstract
Alzheimer’s disease (AD) is a chronic neurodegenerative disease characterized by the accumulation of amyloid plaques and neurofibrillary tangles in the brain. The AD pathophysiology entails chronic inflammation involving innate immune cells including microglia, astrocytes, and other peripheral blood cells. Inflammatory mediators such as cytokines and complements are also linked to AD pathogenesis. Despite increasing evidence supporting the association between abnormal inflammation and AD, no well-established inflammatory biomarkers are currently available for AD. Since many reports have shown that abnormal inflammation precedes the outbreak of the disease, non-invasive and readily available peripheral inflammatory biomarkers should be considered as possible biomarkers for early diagnosis of AD. In this minireview, we introduce the peripheral biomarker candidates related to abnormal inflammation in AD and discuss their possible molecular mechanisms. Furthermore, we also summarize the current state of inflammatory biomarker research in clinical practice and molecular diagnostics. We believe this review will provide new insights into biomarker candidates for the early diagnosis of AD with systemic relevance to inflammation during AD pathogenesis.
참고문헌 (123)
- Heneka MT, "Neuroinflammation in Alzheimer's disease", Lancet Neurol, 14, pp.388~405 (2015)
- Han SH, "Amyloid beta-interacting partners in Alzheimer's disease : From accomplices to possible therapeutic targets", Prog Neurobiol, 137, pp.17~38 (2016)
- Hansen DV, "Microglia in Alzheimer's disease", J Cell Biol, 217, pp.459~472 (2018)
- Cagnin A, "In-vivo measurement of activated microglia in dementia", Lancet, 358, pp.461~467 (2001)
- Baik SH, "A Breakdown in Metabolic Reprogramming Causes Microglia Dysfunction in Alzheimer's Disease", Cell Metab, 30, pp.493~507 e496 (2019)
- Yasojima K, "Up-regulated production and activation of the complement system in Alzheimer's disease brain", Am J Pathol, 154, pp.927~936 (1999)
- Swardfager W, "A meta-analysis of cytokines in Alzheimer's disease", Biol Psychiatry, 68, pp.930~941 (2010)
- Correa JD, "Chemokines in CSF of Alzheimer's disease patients", Arq Neuropsiquiatr, 69, pp.455~459 (2011)
- Sui X, "Cerebrospinal fluid biomarkers of Alzheimer's disease", Neurosci Bull, 30, pp.233~242 (2014)
- Baik SH, "Migration of neutrophils targeting amyloid plaques in Alzheimer's disease mouse model", Neurobiol Aging, 35, pp.1286~1292 (2014)
- Kim MS, "Transfer of a healthy microbiota reduces amyloid and tau pathology in an Alzheimer's disease animal model", Gut, 69, pp.283~294 (2020)
- Akiyama H, "Inflammation and Alzheimer's disease", Neurobiol Aging, 21, pp.383~421 (2000)
- Wilson CJ, "Cytokines and cognition--the case for a head-to-toe inflammatory paradigm", J Am Geriatr Soc, 50, pp.2041~2056 (2002)
- Solfrizzi V, "Circulating biomarkers of cognitive decline and dementia", Clin Chim Acta, 364, pp.91~112 (2006)
- Metcalfe MJ, "Relationship between tau pathology and neuroinflammation in Alzheimer's disease", Mt Sinai J Med, 77, pp.50~58 (2010)
- Holmes C, "Systemic inflammation and disease progression in Alzheimer disease", Neurology, 73, pp.768~774 (2009)
- Leung R, "Inflammatory proteins in plasma are associated with severity of Alzheimer's disease", PLoS One, 8, pp.e64971~ (2013)
- Motta M, "Altered plasma cytokine levels in Alzheimer's disease : correlation with the disease progression", Immunol Lett, 114, pp.46~51 (2007)
- Dionisio-Santos DA, "Exploiting microglial and peripheral immune cell crosstalk to treat Alzheimer's disease", J Neuroinflammation, 16, pp.74~ (2019)
- Dinarello CA, "The role of interleukin-1 in disease", N Engl J Med, 328, pp.106~113 (1993)
- Besedovsky H, "Immunoregulatory feedback between interleukin-1and glucocorticoid hormones", Science, 233, pp.652~654 (1986)
- Shaftel SS, "The role of interleukin-1 in neuroinflammation and Alzheimer disease : an evolving perspective", J Neuroinflammation, 5, pp.7~ (2008)
- Nicklin MJ, "A physical map of the region encompassing the human interleukin-1alpha, interleukin-1 beta, and interleukin-1 receptor antagonist genes", Genomics, 19, pp.382~384 (1994)
- Allan SM, "Interleukin-1and neuronal injury", Nat Rev Immunol, 5, pp.629~640 (2005)
- Patel HC, "Interleukin-1 in the brain : mechanisms of action in acute neurodegeneration", Ann N Y Acad Sci, 992, pp.39~47 (2003)
- Griffin WS, "Brain interleukin 1 and S-100 immunoreactivity are elevated in Down syndrome and Alzheimer disease", Proc Natl Acad Sci U S A, 86, pp.7611~7615 (1989)
- Sheng JG, "Interleukin-1promotion of MAPK-p38 overexpression in experimental animals and in Alzheimer's disease : potential significance for tau protein phosphorylation", Neurochem Int, 39, pp.341~348 (2001)
- Schneider H, "A neuromodulatory role of interleukin-1beta in the hippocampus", Proc Natl Acad Sci U S A, 95, pp.7778~7783 (1998)
- Murray CA, "Evidence that increased hippocampal expression of the cytokine interleukin-1 beta is a common trigger for age-and stress-induced impairments in long-term potentiation", J Neurosci, 18, pp.2974~2981 (1998)
- Li Y, "Neuronal-glial interactions mediated by interleukin-1 enhance neuronal acetylcholinesterase activity and mRNA expression", J Neurosci, 20, pp.149~155 (2000)
- Han SH, "Blood acetylcholinesterase level is a potential biomarker for the early detection of cerebral amyloid deposition in cognitively normal individuals", Neurobiol Aging, 73, pp.21~29 (2019)
- Su F, "Inflammatory Cytokines and Alzheimer's Disease : A Review from the Perspective of Genetic Polymorphisms", Neurosci Bull, 32, pp.469~480 (2016)
- Mrak RE, "Interleukin-1 and the immunogenetics of Alzheimer disease", J Neuropathol Exp Neurol, 59, pp.471~476 (2000)
- Alvarez XA, "Blood levels of histamine, IL-1 beta, and TNF-alpha in patients with mild to moderate Alzheimer disease", Mol Chem Neuropathol, 29, pp.237~252 (1996)
- Licastro F, "Increased plasma levels of interleukin-1, interleukin-6 and alpha-1-antichymotrypsin in patients with Alzheimer's disease: peripheral inflammation or signals from the brain?", J Neuroimmunol, 103, pp.97~102 (2000)
- De Luigi A, "Peripheral inflammatory response in Alzheimer's disease and multiinfarct dementia", Neurobiol Dis, 11, pp.308~314 (2002)
- Forlenza OV, "Increased serum IL-1beta level in Alzheimer's disease and mild cognitive impairment", Dement Geriatr Cogn Disord, 28, pp.507~512 (2009)
- Angelopoulos P, "Cytokines in Alzheimer's disease and vascular dementia", Int J Neurosci, 118, pp.1659~1672 (2008)
- Italiani P, "Circulating levels of IL-1 family cytokines and receptors in Alzheimer's disease: new markers of disease progression?", J Neuroinflammation, 15, pp.342~ (2018)
- Lanzrein AS, "Longitudinal study of inflammatory factors in serum, cerebrospinal fluid, and brain tissue in Alzheimer disease : interleukin-1beta, interleukin-6, interleukin-1 receptor antagonist, tumor necrosis factoralpha, the soluble tumor necrosis factor receptors I and II, and alpha1-antichymotrypsin", Alzheimer Dis Assoc Disord, 12, pp.215~227 (1998)
- Pirttila T, "Alpha 1-antichymotrypsin and IL-1 beta are not increased in CSF or serum in Alzheimer's disease", Neurobiol Aging, 15, pp.313~317 (1994)
- Yasutake C, "Serum BDNF, TNF-alpha and IL-1beta levels in dementia patients : comparison between Alzheimer's disease and vascular dementia", Eur Arch Psychiatry Clin Neurosci, 256, pp.402~406 (2006)
- Bonotis K, "Systemic immune aberrations in Alzheimer's disease patients", J Neuroimmunol, 193, pp.183~187 (2008)
- Bauer J, "Interleukin-6 and alpha-2-macroglobulin indicate an acute-phase state in Alzheimer's disease cortices", FEBS Lett, 285, pp.111~114 (1991)
- Huell M, "Interleukin-6 is present in early stages of plaque formation and is restricted to the brains of Alzheimer's patients", Acta Neuropathol, 89, pp.544~551 (1995)
- Lee KS, "Peripheral cytokines and chemokines in Alzheimer's disease", Dement Geriatr Cogn Disord, 28, pp.281~287 (2009)
- Sun YX, "Inflammatory markers in matched plasma and cerebrospinal fluid from patients with Alzheimer's disease", Dement Geriatr Cogn Disord, 16, pp.136~144 (2003)
- Wu YY, "Alterations of the Neuroinflammatory Markers IL-6 and TRAIL in Alzheimer's Disease", Dement Geriatr Cogn Dis Extra, 5, pp.424~434 (2015)
- Singh VK, "Circulating cytokines in Alzheimer's disease", J Psychiatr Res, 31, pp.657~660 (1997)
- Angelis P, "Serum interleukin-6 and interleukin-6 soluble receptor in Alzheimer's disease", Neurosci Lett, 244, pp.106~108 (1998)
- van Duijn CM, "Serum levels of interleukin-6 are not elevated in patients with Alzheimer's disease", Neurosci Lett, 108, pp.350~354 (1990)
- Garlind A, "Soluble interleukin-1 receptor type II levels are elevated in cerebrospinal fluid in Alzheimer's disease patients", Brain Res, 826, pp.112~116 (1999)
- Tarkowski E, "Cerebral pattern of proand anti-inflammatory cytokines in dementias", Brain Res Bull, 61, pp.255~260 (2003)
- Richartz E, "Decline of immune responsiveness: a pathogenetic factor in Alzheimer's disease?", J Psychiatr Res, 39, pp.535~543 (2005)
- Yamada K, "Concurrent use of granulocyte colony-stimulating factor with low-dose cytosine arabinoside and aclarubicin for previously treated acute myelogenous leukemia : a pilot study", Leukemia, 9, pp.10~14 (1995)
- Papassotiropoulos A, "A genetic variation of the inflammatory cytokine interleukin-6 delays the initial onset and reduces the risk for sporadic Alzheimer's disease", Ann Neurol, 45, pp.666~668 (1999)
- Grimaldi LM, "Association of early-onset Alzheimer's disease with an interleukin-1alpha gene polymorphism", Ann Neurol, 47, pp.361~365 (2000)
- Nicoll JA, "Association of interleukin-1 gene polymorphisms with Alzheimer's disease", Ann Neurol, 47, pp.365~368 (2000)
- Perry VH, "Systemic infections and inflammation affect chronic neurodegeneration", Nat Rev Immunol, 7, pp.161~167 (2007)
- Zhao M, "The induction of the TNFalpha death domain signaling pathway in Alzheimer's disease brain", Neurochem Res, 28, pp.307~318 (2003)
- Lue LF, "Modeling microglial activation in Alzheimer's disease with human postmortem microglial cultures", Neurobiol Aging, 22, pp.945~956 (2001)
- Janelsins MC, "Chronic neuron-specific tumor necrosis factor-alpha expression enhances the local inflammatory environment ultimately leading to neuronal death in 3xTg-AD mice", Am J Pathol, 173, pp.1768~1782 (2008)
- McAlpine FE, "Neuroinflammation and tumor necrosis factor signaling in the pathophysiology of Alzheimer's disease", J Inflamm Res, 1, pp.29~39 (2008)
- Brosseron F, "Body fluid cytokine levels in mild cognitive impairment and Alzheimer's disease : a comparative overview", Mol Neurobiol, 50, pp.534~544 (2014)
- Tarkowski E, "Intracerebral production of tumor necrosis factor-alpha, a local neuroprotective agent, in Alzheimer disease and vascular dementia", J Clin Immunol, 19, pp.223~230 (1999)
- Magaki S, "Increased production of inflammatory cytokines in mild cognitive impairment", Exp Gerontol, 42, pp.233~240 (2007)
- Bruunsgaard H, "A high plasma concentration of TNF-alpha is associated with dementia in centenarians", J Gerontol A Biol Sci Med Sci, 54, pp.M357~364 (1999)
- Fillit H, "Elevated circulating tumor necrosis factor levels in Alzheimer's disease", Neurosci Lett, 129, pp.318~320 (1991)
- Aliberti J, "CCR5provides a signal for microbial induced production of IL-12 by CD8 alpha+ dendritic cells", Nat Immunol, 1, pp.83~87 (2000)
- Schulz O, "CD40triggering of heterodimeric IL-12 p70 production by dendritic cells in vivo requires a microbial priming signal", Immunity, 13, pp.453~462 (2000)
- Chang HD, "The pro-and anti-inflammatory potential of interleukin-12", Ann N Y Acad Sci, 1109, pp.40~46 (2007)
- Rentzos M, "Interleukin-12 is reduced in cerebrospinal fluid of patients with Alzheimer's disease and frontotemporal dementia", J Neurol Sci, 249, pp.110~114 (2006)
- Vom Berg J, "Inhibition of IL-12", IL-23 signaling reduces Alzheimer's disease-like pathology and cognitive decline, 2012, pp.18, 1812~1819
- Town T, "Reduced Th1and enhanced Th2 immunity after immunization with Alzheimer's beta-amyloid(1-42)", J Neuroimmunol, 132, pp.49~59 (2002)
- te Velde AA, "Interleukin-4(IL-4)inhibits secretion of IL-1 beta, tumor necrosis factor alpha, and IL-6 by human monocytes", Blood, 76, pp.1392~1397 (1990)
- Gambi F, "Alzheimer patients treated with an AchE inhibitor show higher IL-4 and lower IL-1 beta levels and expression in peripheral blood mononuclear cells", J Clin Psychopharmacol, 24, pp.314~321 (2004)
- Lugaresi A, "IL-4 in vitro production is upregulated in Alzheimer's disease patients treated with acetylcholinesterase inhibitors", Exp Gerontol, 39, pp.653~657 (2004)
- Strle K, "Interleukin-10 in the brain", Crit Rev Immunol, 21, pp.427~449 (2001)
- Fung TC, "Interactions between the microbiota, immune and nervous systems in health and disease", Nat Neurosci, 20, pp.145~155 (2017)
- Kau AL, "Human nutrition, the gut microbiome and the immune system", Nature, 474, pp.327~336 (2011)
- Karol Kowalski, "Brain-Gut-Microbiota Axis in Alzheimer’s Disease", Journal of Neurogastroenterology and Motility (JNM), 25(1), pp.48~60 (2019), 대한소화기 기능성질환∙운동학회[DOI]
- Bonfili L, "Microbiota modulation counteracts Alzheimer's disease progression influencing neuronal proteolysis and gut hormones plasma levels", Sci Rep, 7, pp.2426~ (2017)
- Arosio B, "Peripheral blood mononuclear cells as a laboratory to study dementia in the elderly", Biomed Res Int, 2014, pp.169203~ (2014)
- Ziegler-Heitbrock L, "The CD14+ CD16+ blood monocytes : their role in infection and inflammation", J Leukoc Biol, 81, pp.584~592 (2007)
- Ciccocioppo F, "The Characterization of Regulatory T-Cell Profiles in Alzheimer's Disease and Multiple Sclerosis", Sci Rep, 9, pp.8788~ (2019)
- Rezai-Zadeh K, "Can peripheral leukocytes be used as Alzheimer's disease biomarkers?", Expert Rev Neurother, 9, pp.1623~1633 (2009)
- Chen SH, "Altered peripheral profile of blood cells in Alzheimer disease: A hospitalbased case-control study", Medicine (Baltimore), 96, pp.e6843~ (2017)
- Lunnon K, "Mitochondrial dysfunction and immune activation are detectable in early Alzheimer's disease blood", J Alzheimers Dis, 30, pp.685~710 (2012)
- Naert G, "A deficiency in CCR2+monocytes : the hidden side of Alzheimer's disease", J Mol Cell Biol, 5, pp.284~293 (2013)
- Richartz-Salzburger E, "Altered lymphocyte distribution in Alzheimer's disease", J Psychiatr Res, 41, pp.174~178 (2007)
- Aiyaz M, "Complement activation as a biomarker for Alzheimer's disease", Immunobiology, 217, pp.204~215 (2012)
- Kolev MV, "Implication of complement system and its regulators in Alzheimer's disease", Curr Neuropharmacol, 7, pp.1~8 (2009)
- Kamboh MI, "Genome-wide association study of Alzheimer's disease", Transl Psychiatry, 2, pp.e117~ (2012)
- Kok EH, "CLU, CR1 and PICALM genes associate with Alzheimer's-related senile plaques", Alzheimers Res Ther, 3, pp.12~ (2011)
- Bradt BM, "Complement-dependent proinflammatory properties of the Alzheimer's disease beta-peptide", J Exp Med, 188, pp.431~438 (1998)
- Hakobyan S, "Complement Biomarkers as Predictors of Disease Progression in Alzheimer's Disease", J Alzheimers Dis, 54, pp.707~716 (2016)
- Weinstein G, "Plasma clusterin levels and risk of dementia, Alzheimer's disease, and stroke", Alzheimers Dement (Amst), 3, pp.103~109 (2016)
- Williams MA, "Plasma Complement factor H in Alzheimer's Disease", J Alzheimers Dis, 45, pp.369~372 (2015)
- Thambisetty M, "Plasma biomarkers of brain atrophy in Alzheimer's disease", PLoS One, 6, pp.e28527~ (2011)
- Haure-Mirande JV, "Integrative approach to sporadic Alzheimer's disease:deficiency of TYROBP in cerebral Abeta amyloidosis mouse normalizes clinical phenotype and complement subnetwork molecular pathology without reducing Abeta burden", Mol Psychiatry, 24, pp.431~446 (2019)
- Efthymiou AG, "Late onset Alzheimer's disease genetics implicates microglial pathways in disease risk", Mol Neurodegener, 12, pp.43~ (2017)
- Lambert JC, "Genome-wide association study identifies variants at CLU and CR1associated with Alzheimer's disease", Nat Genet, 41, pp.1094~1099 (2009)
- Belbin O, "A SNP in the ACT gene associated with astrocytosis and rapid cognitive decline in AD", Neurobiol Aging, 29, pp.1167~1176 (2008)
- Toral-Rios D, "Evaluation of inflammation-related genes polymorphisms in Mexican with Alzheimer's disease : a pilot study", Front Cell Neurosci, 9, pp.148~ (2015)
- Morgan BP, "Complement in the pathogenesis of Alzheimer's disease", Semin Immunopathol, 40, pp.113~124 (2018)
- Jin C, "Association of the CR1 polymorphism with late-onset Alzheimer's disease in Chinese Han populations : a meta-analysis", Neurosci Lett, 527, pp.46~49 (2012)
- Liu G, "The CLU gene rs11136000 variant is significantly associated with Alzheimer's disease in Caucasian and Asian populations", Neuromolecular Med, 16, pp.52~60 (2014)
- Zhu R, "Association between CLU gene rs11136000 polymorphism and Alzheimer's disease : an updated meta-analysis", Neurol Sci, 39, pp.679~689 (2018)
- Tan L, "Effect of CLU genetic variants on cerebrospinal fluid and neuroimaging markers in healthy, mild cognitive impairment and Alzheimer's disease cohorts", Sci Rep, 6, pp.26027~ (2016)
- Xing YY, "Blood clusterin levels, rs9331888 polymorphism, and the risk of Alzheimer's disease", J Alzheimers Dis, 29, pp.515~519 (2012)
- Zhou J, "Complement C3 and C4 expression in C1q sufficient and deficient mouse models of Alzheimer's disease", J Neurochem, 106, pp.2080~2092 (2008)
- Fonseca MI, "Analysis of the Putative Role of CR1 in Alzheimer's Disease : Genetic Association, Expression and Function", PLoS One, 11, pp.e0149792~ (2016)
- Foster EM, "Clusterin in Alzheimer's Disease : Mechanisms, Genetics, and Lessons From Other Pathologies", Front Neurosci, 13, pp.164~ (2019)
- Thambisetty M, "Association of plasma clusterin concentration with severity, pathology, and progression in Alzheimer disease", Arch Gen Psychiatry, 67, pp.739~748 (2010)
- Jongbloed W, "Clusterin Levels in Plasma Predict Cognitive Decline and Progression to Alzheimer's Disease", J Alzheimers Dis, 46, pp.1103~1110 (2015)
- Winston CN, "Complement protein levels in plasma astrocyte-derived exosomes are abnormal in conversion from mild cognitive impairment to Alzheimer's disease dementia", Alzheimers Dement(Amst), 11, pp.61~66 (2019)
- Daborg J, "Cerebrospinal fluid levels of complement proteins C3, C4 and CR1 in Alzheimer's disease", J Neural Transm(Vienna), 119, pp.789~797 (2012)
- Bennett S, "Plasma levels of complement 4a protein are increased in Alzheimer's disease", Alzheimer Dis Assoc Disord, 26, pp.329~334 (2012)
- Yarchoan M, "Association of plasma C-reactive protein levels with the diagnosis of Alzheimer's disease", J Neurol Sci, 333, pp.9~12 (2013)
- Locascio JJ, "Plasma amyloid beta-protein and C-reactive protein in relation to the rate of progression of Alzheimer disease", Arch Neurol, 65, pp.776~785 (2008)
- Watanabe Y, "Elevated C-Reactive Protein Is Associated with Cognitive Decline in Outpatients of a General Hospital : The Project in Sado for Total Health(PROST)", Dement Geriatr Cogn Dis Extra, 6, pp.10~19 (2016)
- Vintimilla R, "The relationship of CRP and cognition in cognitively normal older Mexican Americans : A cross-sectional study of the HABLE cohort", Medicine (Baltimore), 98, pp.e15605~ (2019)
- Park JC, "Chemically treated plasma Abeta is a potential blood-based biomarker for screening cerebral amyloid deposition", Alzheimers Res Ther, 9, pp.20~ (2017)
