본문 바로가기
KERD
논문KCI 등재

Promising Blood Biomarkers for Clinical Use in Alzheimer’s Disease: A Focused Update

1

조회

0

다운로드

5

인용

0

참고문헌

키워드

초록

Alzheimer’s disease (AD) is the most-common cause of neurodegenerative dementia, and it is characterized by abnormal amyloid and tau accumulation, which indicates neurodegeneration. AD has mostly been diagnosed clinically. However, ligand-specific positron emission tomography (PET) imaging, such as amyloid PET, and cerebrospinal fluid (CSF) biomarkers are needed to accurately diagnose AD, since they supplement the shortcomings of clinical diagnoses. Using biomarkers that represent the pathology of AD is essential (particularly when disease-modifying treatment is available) to identify the corresponding pathology of targeted therapy and for monitoring the treatment response. Although imaging and CSF biomarkers are useful, their widespread use is restricted by their high cost and the discomfort during the lumbar puncture, respectively. Recent advances in AD blood biomarkers shed light on their future use for clinical purposes. The amyloid β (Aβ)42/Aβ40 ratio and the concentrations of phosphorylated tau at threonine 181 and at threonine 217, and of neurofilament light in the blood were found to represent the pathology of Aβ, tau, and neurodegeneration in the brain when using automatic electrochemiluminescence technologies, single-molecule arrays, immunoprecipitation coupled with mass spectrometry, etc. These blood biomarkers are imminently expected to be incorporated into clinical practice to predict, diagnose, and determine the stage of AD. In this review we focus on advancements in the measurement technologies for blood biomarkers and the promising biomarkers that are approaching clinical application. We also discuss the current limitations, the needed further investigations, and the perspectives on their use.

Abstract

Alzheimer’s disease (AD) is the most-common cause of neurodegenerative dementia, and it is characterized by abnormal amyloid and tau accumulation, which indicates neurodegeneration. AD has mostly been diagnosed clinically. However, ligand-specific positron emission tomography (PET) imaging, such as amyloid PET, and cerebrospinal fluid (CSF) biomarkers are needed to accurately diagnose AD, since they supplement the shortcomings of clinical diagnoses. Using biomarkers that represent the pathology of AD is essential (particularly when disease-modifying treatment is available) to identify the corresponding pathology of targeted therapy and for monitoring the treatment response. Although imaging and CSF biomarkers are useful, their widespread use is restricted by their high cost and the discomfort during the lumbar puncture, respectively. Recent advances in AD blood biomarkers shed light on their future use for clinical purposes. The amyloid β (Aβ)42/Aβ40 ratio and the concentrations of phosphorylated tau at threonine 181 and at threonine 217, and of neurofilament light in the blood were found to represent the pathology of Aβ, tau, and neurodegeneration in the brain when using automatic electrochemiluminescence technologies, single-molecule arrays, immunoprecipitation coupled with mass spectrometry, etc. These blood biomarkers are imminently expected to be incorporated into clinical practice to predict, diagnose, and determine the stage of AD. In this review we focus on advancements in the measurement technologies for blood biomarkers and the promising biomarkers that are approaching clinical application. We also discuss the current limitations, the needed further investigations, and the perspectives on their use.

참고문헌 (78)

  1. Wilson MR, "Potential roles of abundant extracellular chaperones in the control of amyloid formation and toxicity", Mol Biosyst, 4, pp.42~52 (2008)
  2. Chen M, "Platelets are the primary source of amyloid beta-peptide in human blood", Biochem Biophys Res Commun, 213, pp.96~103 (1995)
  3. Kent SA, "The physiological roles of tau and Aβ : implications for Alzheimer’s disease pathology and therapeutics", Acta Neuropathol, 140, pp.417~447 (2020)
  4. Barthélemy NR, "Blood plasma phosphorylated-tau isoforms track CNS change in Alzheimer’s disease", J Exp Med, 217, pp.e20200861~ (2020)
  5. Jack CR Jr, "NIA-AA research framework : toward a biological definition of Alzheimer’s disease", Alzheimers Dement, 14, pp.535~562 (2018)
  6. Cummings J, "The"rights"of precision drug development for Alzheimer’s disease", Alzheimers Res Ther, 11, pp.76~ (2019)
  7. Sevigny J, "The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease", Nature, 537, pp.50~56 (2016)
  8. "Aducanumab (marketed as Aduhelm) information" (2021)[URL]
  9. Hampel H, "Developing the ATX(N)classification for use across the Alzheimer disease continuum", Nat Rev Neurol, 17, pp.580~589 (2021)
  10. Koychev I, "Blood-based ATN biomarkers of Alzheimer’s disease : a meta-analysis", J Alzheimers Dis, 79, pp.177~195 (2021)
  11. Mattsson N, "CSF biomarkers and incipient Alzheimer disease in patients with mild cognitive impairment", JAMA, 302, pp.385~393 (2009)
  12. Mulder C, "Amyloid-beta(1-42), total tau, and phosphorylated tau as cerebrospinal fluid biomarkers for the diagnosis of Alzheimer disease", Clin Chem, 56, pp.248~253 (2010)
  13. Park SA, "Cerebrospinal fluid biomarkers for the diagnosis of Alzheimer disease in South Korea", Alzheimer Dis Assoc Disord, 31, pp.13~18 (2017)
  14. Palmqvist S, "Cerebrospinal fluid and plasma biomarker trajectories with increasing amyloid deposition in Alzheimer’s disease", EMBO Mol Med, 11, pp.e11170~ (2019)
  15. Olsson B, "CSF and blood biomarkers for the diagnosis of Alzheimer’s disease : a systematic review and meta-analysis", Lancet Neurol, 15, pp.673~684 (2016)
  16. Hansson O, "CSF biomarkers of Alzheimer’s disease concord with amyloid-βPET and predict clinical progression : a study of fully automated immunoassays in BioFINDER and ADNI cohorts", Alzheimers Dement, 14, pp.1470~1481 (2018)
  17. Kaplow J, "Concordance of Lumipulse cerebrospinal fluid t-tau", Aβ42 ratio with amyloid PET status, 2020, pp.16, 144~152
  18. Kuhle J, "Comparison of three analytical platforms for quantification of the neurofilament light chain in blood samples : ELISA, electrochemiluminescence immunoassay and Simoa", Clin Chem Lab Med, 54, pp.1655~1661 (2016)
  19. Janelidze S, "Head-to-head comparison of 8 plasma amyloid-β 42", 40assays in Alzheimer disease, 2021, pp.78, 1375~1382
  20. Mielke MM, "Plasma phospho-tau181 increases with Alzheimer’s disease clinical severity and is associated with tau-and amyloid-positron emission tomography", Alzheimers Dement, 14, pp.989~997 (2018)
  21. Lue LF, "Advance in plasma AD core biomarker development : current findings from immunomagnetic reductionbased SQUID technology", Neurol Ther, 8(Suppl 2), pp.95~111 (2019)
  22. "Taiwan FDA approves MagQu plasma Aβ and tau tests" (2021)[URL]
  23. Portelius E, "Proteomic studies of cerebrospinal fluid biomarkers of Alzheimer’s disease : an update", Expert Rev Proteomics, 14, pp.1007~1020 (2017)
  24. Nakamura A, "High performance plasma amyloid-β biomarkers for Alzheimer’s disease", Nature, 554, pp.249~254 (2018)
  25. Ovod V, "Amyloid β concentrations and stable isotope labeling kinetics of human plasma specific to central nervous system amyloidosis", Alzheimers Dement, 13, pp.841~849 (2017)
  26. "Plasma Aβ test wins approval—Are p-tau tests far behind?" (2020)[URL]
  27. An SSA, "Dynamic changes of oligomeric amyloid β levels in plasma induced by spiked synthetic Aβ42", Alzheimers Res Ther, 9, pp.86~ (2017)
  28. Wang MJ, "Oligomeric forms of amyloid-β protein in plasma as a potential blood-based biomarker for Alzheimer’s disease", Alzheimers Res Ther, 9, pp.98~ (2017)
  29. Babapour Mofrad R, "Plasma amyloid-β oligomerization assay as a pre-screening test for amyloid status", Alzheimers Res Ther, 13, pp.133~ (2021)
  30. Keshavan A, "Population-based blood screening for preclinical Alzheimer’s disease in a British birth cohort at age 70", Brain, 144, pp.434~449 (2021)
  31. Hyman BT, "National Institute on Aging-Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease", Alzheimers Dement, 8, pp.1~13 (2012)
  32. Fagan AM, "Cerebrospinal fluid tau", beta-amyloid(42)ratio as a prediction of cognitive decline in nondemented older adults, 2007, pp.64, 343~349
  33. Rowe CC, "Brain amyloid imaging", J Nucl Med, 52, pp.1733~1740 (2011)
  34. Chouraki V, "Plasma amyloid-β and risk of Alzheimer’s disease in the Framingham Heart Study", Alzheimers Dement, 11, pp.249~257 (2015)
  35. Hansson O, "Evaluation of plasma Abeta(40)and Abeta(42)as predictors of conversion to Alzheimer’s disease in patients with mild cognitive impairment", Neurobiol Aging, 31, pp.357~367 (2010)
  36. Toledo JB, "Factors affecting Aβ plasma levels and their utility as biomarkers in ADNI", Acta Neuropathol, 122, pp.401~413 (2011)
  37. Kim HJ, "Elevation of the plasma Aβ40", Aβ42 ratio as a diagnostic marker of sporadic earlyonset Alzheimer’s disease, 2015, pp.48, 1043~1050
  38. Jansen WJ, "Prevalence of cerebral amyloid pathology in persons without dementia : a meta-analysis", JAMA, 313, pp.1924~1938 (2015)
  39. Serrano-Pozo A, "Mild to moderate Alzheimer dementia with insufficient neuropathological changes", Ann Neurol, 75, pp.597~601 (2014)
  40. Schindler SE, "High-precision plasma β-amyloid 42", 40 predicts current and future brain amyloidosis, 2019, pp.93, e1647~e1659
  41. Janelidze S, "Plasma β-amyloid in Alzheimer’s disease and vascular disease", Sci Rep, 6, pp.26801~ (2016)
  42. Chiu MJ, "Nanoparticlebased immunomagnetic assay of plasma biomarkers for differentiating dementia and prodromal states of Alzheimer’s disease-A crossvalidation study", Nanomedicine, 28, pp.102182~ (2020)
  43. Blennow K, "Cerebrospinal fluid and plasma biomarkers in Alzheimer disease", Nat Rev Neurol, 6, pp.131~144 (2010)
  44. Teunissen CE, "Plasma amyloid-β(Aβ 42)correlates with cerebrospinal fluid Aβ42 in Alzheimer’s disease", J Alzheimers Dis, 62, pp.1857~1863 (2018)
  45. Janelidze S, "Plasma P-tau181 in Alzheimer’s disease : relationship to other biomarkers, differential diagnosis, neuropathology and longitudinal progression to Alzheimer’s dementia", Nat Med, 26, pp.379~386 (2020)
  46. Lantero Rodriguez J, "Plasma p-tau181 accurately predicts Alzheimer’s disease pathology at least 8 years prior to post-mortem and improves the clinical characterisation of cognitive decline", Acta Neuropathol, 140, pp.267~278 (2020)
  47. Thijssen EH, "Plasma phosphorylated tau 217 and phosphorylated tau 181 as biomarkers in Alzheimer’s disease and frontotemporal lobar degeneration : a retrospective diagnostic performance study", Lancet Neurol, 20, pp.739~752 (2021)
  48. Mattsson-Carlgren N, "Longitudinal plasma p-tau217 is increased in early stages of Alzheimer’s disease", Brain, 143, pp.3234~3241 (2020)
  49. Palmqvist S, "Discriminative accuracy of plasma phospho-tau217 for Alzheimer disease vs other neurodegenerative disorders", JAMA, 324, pp.772~781 (2020)
  50. Janelidze S, "Associations of plasma phospho-Tau217 levels with tau positron emission tomography in early Alzheimer disease", JAMA Neurol, 78, pp.149~156 (2021)
  51. Palmqvist S, "Prediction of future Alzheimer’s disease dementia using plasma phospho-tau combined with other accessible measures", Nat Med, 27, pp.1034~1042 (2021)
  52. Ashton NJ, "Plasma p-tau231 : a new biomarker for incipient Alzheimer’s disease pathology", Acta Neuropathol, 141, pp.709~724 (2021)
  53. Mielke MM, "Comparison of plasma phosphorylated tau species with amyloid and tau positron emission tomography, neurodegeneration, vascular pathology, and cognitive outcomes", JAMA Neurol, 78, pp.1108~1117 (2021)
  54. Brickman AM, "Plasma p-tau181, p-tau217, and other blood-based Alzheimer’s disease biomarkers in a multi-ethnic, community study", Alzheimers Dement, 17, pp.1353~1364 (2021)
  55. Yuan A, "Neurofilament proteins as biomarkers to monitor neurological diseases and the efficacy of therapies", Front Neurosci, 15, pp.689938~ (2021)
  56. Alagaratnam J, "Correlation between CSF and blood neurofilament light chain protein : a systematic review and meta-analysis", BMJ Neurol Open, 3, pp.e000143~ (2021)
  57. Ashton NJ, "A multicentre validation study of the diagnostic value of plasma neurofilament light", Nat Commun, 12, pp.3400~ (2021)
  58. Barro C, "Neurological symptoms and blood neurofilament light levels", Acta Neurol Scand, 144, pp.13~20 (2021)
  59. Mattsson N, "Association between longitudinal plasma neurofilament light and neurodegeneration in patients with Alzheimer disease", JAMA Neurol, 76, pp.791~799 (2019)
  60. Preische O, "Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer’s disease", Nat Med, 25, pp.277~283 (2019)
  61. Weston PS, "Longitudinal measurement of serum neurofilament light in presymptomatic familial Alzheimer’s disease", Alzheimers Res Ther, 11, pp.19~ (2019)
  62. Pereira JB, "Association between cerebrospinal fluid and plasma neurodegeneration biomarkers with brain atrophy in Alzheimer’s disease", Neurobiol Aging, 58, pp.14~29 (2017)
  63. Quiroz YT, "Plasma neurofilament light chain in the presenilin 1 E280A autosomal dominant Alzheimer’s disease kindred : a cross-sectional and longitudinal cohort study", Lancet Neurol, 19, pp.513~521 (2020)
  64. Xiao Z, "Plasma biomarker profiles and the correlation with cognitive function across the clinical spectrum of Alzheimer’s disease", Alzheimers Res Ther, 13, pp.123~ (2021)
  65. 박선아, "New fluid biomarkers tracking non-amyloid-β and non-tau pathology in Alzheimer’s disease", Experimental and Molecular Medicine, 52, pp.1~13 (2020), 생화학분자생물학회[DOI]
  66. Pase MP, "Assessment of plasma total tau level as a predictive biomarker for dementia and related endophenotypes", JAMA Neurol, 76, pp.598~606 (2019)
  67. Ding X, "Ultrasensitive assays for detection of plasma tau and phosphorylated tau 181 in Alzheimer’s disease : a systematic review and meta-analysis", Transl Neurodegener, 10, pp.10~ (2021)
  68. Illán-Gala I, "Plasma tau and neurofilament light in frontotemporal lobar degeneration and Alzheimer disease", Neurology, 96, pp.e671~e683 (2021)
  69. Sugarman MA, "A longitudinal examination of plasma neurofilament light and total tau for the clinical detection and monitoring of Alzheimer’s disease", Neurobiol Aging, 94, pp.60~70 (2020)
  70. Cullen NC, "Plasma biomarkers of Alzheimer’s disease improve prediction of cognitive decline in cognitively unimpaired elderly populations", Nat Commun, 12, pp.3555~ (2021)
  71. Korley FK, "Serum NfL(neurofilament light chain)levels and incident stroke in adults with diabetes mellitus", Stroke, 50, pp.1669~1675 (2019)
  72. Akamine S, "Renal function is associated with blood neurofilament light chain level in older adults", Sci Rep, 10, pp.20350~ (2020)
  73. Khalil M, "Serum neurofilament light levels in normal aging and their association with morphologic brain changes", Nat Commun, 11, pp.812~ (2020)
  74. Boulo S, "First amyloid β1-42 certified reference material for re-calibrating commercial immunoassays", Alzheimers Dement, 16, pp.1493~1503 (2020)
  75. Hansson O, "Biomarkers for neurodegenerative diseases", Nat Med, 27, pp.954~963 (2021)
  76. Zetterberg H, "Biomarkers for Alzheimer’s disease-preparing for a new era of disease-modifying therapies", Mol Psychiatry, 26, pp.296~308 (2021)
  77. Janelidze S, "Detecting amyloid positivity in early Alzheimer’s disease using combinations of plasma Aβ42", Aβ40 and p-tau, 2022, pp.18, 283~293
  78. Benedet AL, "Stage-specific links between plasma neurofilament light and imaging biomarkers of Alzheimer’s disease", Brain, 143, pp.3793~3804 (2020)

관련 논문AI추천

이 간행물의 다른 논문 (17건)