The validation status of blood biomarkers of amyloid and phospho-tau assessed with the 5-phase development framework for AD biomarkers.
Alzheimer’s disease
Aβ40
Aβ42
Blood
P-tau
Strategic roadmap
Journal
European journal of nuclear medicine and molecular imaging
ISSN: 1619-7089
Titre abrégé: Eur J Nucl Med Mol Imaging
Pays: Germany
ID NLM: 101140988
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
received:
03
11
2020
accepted:
09
02
2021
pubmed:
8
3
2021
medline:
29
6
2021
entrez:
7
3
2021
Statut:
ppublish
Résumé
The development of blood biomarkers that reflect Alzheimer's disease (AD) pathophysiology (phosphorylated tau and amyloid-β) has offered potential as scalable tests for dementia differential diagnosis and early detection. In 2019, the Geneva AD Biomarker Roadmap Initiative included blood biomarkers in the systematic validation of AD biomarkers. A panel of experts convened in November 2019 at a two-day workshop in Geneva. The level of maturity (fully achieved, partly achieved, preliminary evidence, not achieved, unsuccessful) of blood biomarkers was assessed based on the Biomarker Roadmap methodology and discussed fully during the workshop which also evaluated cerebrospinal fluid (CSF) and positron emission tomography (PET) biomarkers. Plasma p-tau has shown analytical validity (phase 2 primary aim 1) and first evidence of clinical validity (phase 3 primary aim 1), whereas the maturity level for Aβ remains to be partially achieved. Full and partial achievement has been assigned to p-tau and Aβ, respectively, in their associations to ante-mortem measures (phase 2 secondary aim 2). However, only preliminary evidence exists for the influence of covariates, assay comparison and cut-off criteria. Despite the relative infancy of blood biomarkers, in comparison to CSF biomarkers, much has already been achieved for phases 1 through 3 - with p-tau having greater success in detecting AD and predicting disease progression. However, sufficient data about the effect of covariates on the biomarker measurement is lacking. No phase 4 (real-world performance) or phase 5 (assessment of impact/cost) aim has been tested, thus not achieved.
Identifiants
pubmed: 33677733
doi: 10.1007/s00259-021-05253-y
pii: 10.1007/s00259-021-05253-y
pmc: PMC8175325
doi:
Substances chimiques
Amyloid beta-Peptides
0
Biomarkers
0
Peptide Fragments
0
tau Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
2140-2156Références
Pepe MS, Etzioni R, Feng Z, Potter JD, Thompson ML, Thornquist M, et al. Phases of biomarker development for early detection of cancer. J Natl Cancer Inst. 2001;93(14):1054–61.
pubmed: 11459866
Boccardi M, Gallo V, Yasui Y, Vineis P, Padovani A, Mosimann U, et al. The biomarker-based diagnosis of Alzheimer's disease. 2-lessons from oncology. Neurobiol Aging. 2017;52:141–52.
pubmed: 28317645
Frisoni GB, Perani D, Bastianello S, Bernardi G, Porteri C, Boccardi M, et al. Biomarkers for the diagnosis of Alzheimer's disease in clinical practice: an Italian intersocietal roadmap. Neurobiol Aging. 2017;52:119–31.
pubmed: 28317643
Cerami C, Dubois B, Boccardi M, Monsch AU, Demonet JF, Cappa SF, et al. Clinical validity of delayed recall tests as a gateway biomarker for Alzheimer's disease in the context of a structured 5-phase development framework. Neurobiol Aging. 2017;52:153–66.
pubmed: 28317646
Ten Kate M, Barkhof F, Boccardi M, Visser PJ, Jack CR Jr, Lovblad KO, et al. Clinical validity of medial temporal atrophy as a biomarker for Alzheimer's disease in the context of a structured 5-phase development framework. Neurobiol Aging. 2017;52:167–82 e1.
pubmed: 28317647
Garibotto V, Herholz K, Boccardi M, Picco A, Varrone A, Nordberg A, et al. Clinical validity of brain fluorodeoxyglucose positron emission tomography as a biomarker for Alzheimer's disease in the context of a structured 5-phase development framework. Neurobiol Aging. 2017;52:183–95.
pubmed: 28317648
Chiotis K, Saint-Aubert L, Boccardi M, Gietl A, Picco A, Varrone A, et al. Clinical validity of increased cortical uptake of amyloid ligands on PET as a biomarker for Alzheimer's disease in the context of a structured 5-phase development framework. Neurobiol Aging. 2017;52:214–27.
pubmed: 28317650
Sonni I, Ratib O, Boccardi M, Picco A, Herholz K, Nobili F, et al. Clinical validity of presynaptic dopaminergic imaging with (123)I-ioflupane and noradrenergic imaging with (123)I-MIBG in the differential diagnosis between Alzheimer's disease and dementia with Lewy bodies in the context of a structured 5-phase development framework. Neurobiol Aging. 2017;52:228–42.
pubmed: 28317651
Mattsson N, Lonneborg A, Boccardi M, Blennow K, Hansson O, B. Geneva Task Force for the Roadmap of Alzheimer's. Clinical validity of cerebrospinal fluid Abeta42, tau, and phospho-tau as biomarkers for Alzheimer's disease in the context of a structured 5-phase development framework. Neurobiol Aging. 2017;52:196–213.
pubmed: 28317649
Leuzy A, Ashton NJ, Mattsson-Carlgren N, Dodich A, Boccardi M, Corre11 J, et al. 2020 update on the clinical validity of cerebrospinal fluid amyloid, tau, and phospho-tau as biomarkers for Alzheimer’s disease in the context of a structured 5-phase development framework. 2021. https://doi.org/10.1007/s00259-021-05258-7 .
Olsson B, Lautner R, Andreasson U, Ohrfelt A, Portelius E, Bjerke M, et al. CSF and blood biomarkers for the diagnosis of Alzheimer's disease: a systematic review and meta-analysis. Lancet Neurol. 2016;15(7):673–84.
pubmed: 27068280
Hye A, Lynham S, Thambisetty M, Causevic M, Campbell J, Byers HL, et al. Proteome-based plasma biomarkers for Alzheimer's disease. Brain. 2006;129(Pt 11):3042–50.
pubmed: 17071923
Shi L, Baird AL, Westwood S, Hye A, Dobson R, Thambisetty M, et al. A decade of blood biomarkers for Alzheimer's disease research: an evolving field, improving study designs, and the challenge of replication. J Alzheimers Dis. 2018;62(3):1181–98.
pubmed: 29562526
pmcid: 5870012
Ray S, Britschgi M, Herbert C, Takeda-Uchimura Y, Boxer A, Blennow K, et al. Classification and prediction of clinical Alzheimer's diagnosis based on plasma signaling proteins. Nat Med. 2007;13(11):1359–62.
pubmed: 17934472
Mapstone M, Cheema AK, Fiandaca MS, Zhong X, Mhyre TR, MacArthur LH, et al. Plasma phospholipids identify antecedent memory impairment in older adults. Nat Med. 2014;20(4):415–8.
pubmed: 24608097
pmcid: 5360460
Westwood S, Baird AL, Hye A, Ashton NJ, Nevado-Holgado AJ, Anand SN, et al. Plasma protein biomarkers for the prediction of CSF amyloid and tau and [(18)F]-flutemetamol PET scan result. Front Aging Neurosci. 2018;10:409.
pubmed: 30618716
pmcid: 6297196
Westwood S, Baird AL, Anand SN, Nevado-Holgado AJ, Kormilitzin A, Shi L, et al. Validation of plasma proteomic biomarkers relating to brain amyloid burden in the EMIF-Alzheimer's disease multimodal biomarker discovery cohort. J Alzheimers Dis. 2020;74(1):213–25.
pubmed: 31985466
pmcid: 7175945
Ashton NJ, Nevado-Holgado AJ, Barber IS, Lynham S, Gupta V, Chatterjee P, et al. A plasma protein classifier for predicting amyloid burden for preclinical Alzheimer's disease. Sci Adv. 2019;5(2):eaau7220.
pubmed: 30775436
pmcid: 6365111
Blennow K, Zetterberg H. Biomarkers for Alzheimer's disease: current status and prospects for the future. J Intern Med. 2018;284(6):643–63.
pubmed: 30051512
Ashton NJ, Hye A, Rajkumar AP, Leuzy A, Snowden S, Suarez-Calvet M, et al. An update on blood-based biomarkers for non-Alzheimer neurodegenerative disorders. Nat Rev Neurol. 2020;16(5):265–84.
pubmed: 32322100
Mattsson N, Andreasson U, Zetterberg H, Blennow K, I. Alzheimer's Disease Neuroimaging. Association of Plasma Neurofilament Light With Neurodegeneration in Patients With Alzheimer Disease. JAMA Neurol. 2017;74(5):557–66.
pubmed: 28346578
pmcid: 5822204
Mattsson N, Cullen NC, Andreasson U, Zetterberg H, Blennow K. Association between longitudinal plasma neurofilament light and neurodegeneration in patients with Alzheimer disease. JAMA Neurol. 2019;76(7):791–9.
pubmed: 31009028
pmcid: 6583067
Ashton NJ, Leuzy A, Lim YM, Troakes C, Hortobagyi T, Hoglund K, et al. Increased plasma neurofilament light chain concentration correlates with severity of post-mortem neurofibrillary tangle pathology and neurodegeneration. Acta Neuropathol Commun. 2019;7(1):5.
pubmed: 30626432
pmcid: 6327431
Benedet AL, Ashton NJ, Pascoal TA, Leuzy A, Mathotaarachchi S, Kang MS, et al. Plasma neurofilament light associates with Alzheimer's disease metabolic decline in amyloid-positive individuals. Alzheimers Dement (Amst). 2019;11:679–89.
pmcid: 6816316
Simrén J, Leuzy A, Karikari TK, Hye A, Benedet AL, Lantero-Rodriguez J, et al. The diagnostic and prognostic capabilities of plasma biomarkers in Alzheimer's disease. Alzheimers Dement. 2021. https://doi.org/10.1002/alz.12283 .
Hansson O, Janelidze S, Hall S, Magdalinou N, Lees AJ, Andreasson U, et al. Blood-based NfL: a biomarker for differential diagnosis of parkinsonian disorder. Neurology. 2017;88(10):930–7.
pubmed: 28179466
pmcid: 5333515
Ashton NJ, Janelidze S, Al-Khleifat A, Leuzy A, Van der Ende EL, Karikari TK, et al. Diagnostic value of plasma neurofilament light: a multicentre validation study. Research Square. 2020. https://doi.org/10.21203/rs.3.rs-63386/v1 (PREPRINT (Version 1)).
Wihersaari L, Ashton NJ, Reinikainen M, Jakkula P, Pettila V, Hastbacka J, et al. Neurofilament light as an outcome predictor after cardiac arrest: a post hoc analysis of the COMACARE trial. Intensive Care Med. 2020. https://doi.org/10.1007/s00134-020-06218-9 .
Mattsson N, Zetterberg H, Janelidze S, Insel PS, Andreasson U, Stomrud E, et al. Plasma tau in Alzheimer disease. Neurology. 2016;87(17):1827–35.
pubmed: 27694257
pmcid: 5089525
Zetterberg H, Wilson D, Andreasson U, Minthon L, Blennow K, Randall J, et al. Plasma tau levels in Alzheimer's disease. Alzheimers Res Ther. 2013;5(2):9.
pubmed: 23551972
pmcid: 3707015
Chen Z, Mengel D, Keshavan A, Rissman RA, Billinton A, Perkinton M, et al. Learnings about the complexity of extracellular tau aid development of a blood-based screen for Alzheimer's disease. Alzheimers Dement. 2019;15(3):487–96.
pubmed: 30419228
Mengel D, Janelidze S, Glynn RJ, Liu W, Hansson O, Walsh DM. Plasma NT1 tau is a specific and early marker of Alzheimer's disease. Ann Neurol. 2020;88(5):878–92.
pubmed: 32829532
Boccardi M, Dodich A, Albanese E, Gayet-Ageron A, Festari C, Ramusino M, et al. The strategic biomarker roadmap for the validation of Alzheimer’s diagnostic biomarkers: methodological update. EJNMMI. 2021. https://doi.org/10.1007/s00259-020-05120-2 .
Jack CR Jr, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, et al. NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease. Alzheimers Dement. 2018;14(4):535–62.
pubmed: 29653606
pmcid: 5958625
McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA work group under the auspices of Department of Health and Human Services Task Force on Alzheimer's disease. Neurology. 1984;34(7):939–44.
pubmed: 6610841
Beach TG, Monsell SE, Phillips LE, Kukull W. Accuracy of the clinical diagnosis of Alzheimer disease at National Institute on Aging Alzheimer Disease Centers, 2005-2010. J Neuropathol Exp Neurol. 2012;71(4):266–73.
pubmed: 22437338
pmcid: 3331862
Bennett DA, Wilson RS, Schneider JA, Evans DA, Beckett LA, Aggarwal NT, et al. Natural history of mild cognitive impairment in older persons. Neurology. 2002;59(2):198–205.
pubmed: 12136057
Jack CR Jr, Lowe VJ, Senjem ML, Weigand SD, Kemp BJ, Shiung MM, et al. 11C PiB and structural MRI provide complementary information in imaging of Alzheimer's disease and amnestic mild cognitive impairment. Brain. 2008;131(Pt 3):665–80.
pubmed: 18263627
pmcid: 2730157
Dubois B, Feldman HH, Jacova C, Hampel H, Molinuevo JL, Blennow K, et al. Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria. Lancet Neurol. 2014;13(6):614–29.
pubmed: 24849862
Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, et al. The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011;7(3):270–9.
pubmed: 21514249
pmcid: 3312027
Masters CL, Simms G, Weinman NA, Multhaup G, McDonald BL, Beyreuther K. Amyloid plaque core protein in Alzheimer disease and Down syndrome. Proc Natl Acad Sci U S A. 1985;82(12):4245–9.
pubmed: 3159021
pmcid: 397973
Jarrett JT, Berger EP, Lansbury PT Jr. The carboxy terminus of the beta amyloid protein is critical for the seeding of amyloid formation: implications for the pathogenesis of Alzheimer's disease. Biochemistry. 1993;32(18):4693–7.
pubmed: 8490014
Grundke-Iqbal I, Iqbal K, Quinlan M, Tung YC, Zaidi MS, Wisniewski HM. Microtubule-associated protein tau. A component of Alzheimer paired helical filaments. J Biol Chem. 1986;261(13):6084–9.
pubmed: 3084478
Grundke-Iqbal I, Iqbal K, Tung YC, Quinlan M, Wisniewski HM, Binder LI. Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology. Proc Natl Acad Sci U S A. 1986;83(13):4913–7.
pubmed: 3088567
pmcid: 323854
Seubert P, Vigo-Pelfrey C, Esch F, Lee M, Dovey H, Davis D, et al. Isolation and quantification of soluble Alzheimer's beta-peptide from biological fluids. Nature. 1992;359(6393):325–7.
pubmed: 1406936
Motter R, Vigo-Pelfrey C, Kholodenko D, Barbour R, Johnson-Wood K, Galasko D, et al. Reduction of beta-amyloid peptide42 in the cerebrospinal fluid of patients with Alzheimer's disease. Ann Neurol. 1995;38(4):643–8.
pubmed: 7574461
Shoji M, Matsubara E, Kanai M, Watanabe M, Nakamura T, Tomidokoro Y, et al. Combination assay of CSF tau, a beta 1-40 and a beta 1-42(43) as a biochemical marker of Alzheimer's disease. J Neurol Sci. 1998;158(2):134–40.
pubmed: 9702683
Blennow K, Wallin A, Agren H, Spenger C, Siegfried J, Vanmechelen E. Tau protein in cerebrospinal fluid: a biochemical marker for axonal degeneration in Alzheimer disease? Mol Chem Neuropathol. 1995;26(3):231–45.
pubmed: 8748926
Iqbal K, Grundke-Iqbal I. Elevated levels of tau and ubiquitin in brain and cerebrospinal fluid in Alzheimer's disease. Int Psychogeriatr. 1997;9(Suppl 1):289–96 discussion 317-21.
pubmed: 9447449
Ashton NJ, Scholl M, Heurling K, Gkanatsiou E, Portelius E, Hoglund K, et al. Update on biomarkers for amyloid pathology in Alzheimer's disease. Biomark Med. 2018;12(7):799–812.
pubmed: 29902934
Janelidze S, Pannee J, Mikulskis A, Chiao P, Zetterberg H, Blennow K, et al. Concordance between different amyloid immunoassays and visual amyloid positron emission tomographic assessment. JAMA Neurol. 2017;74(12):1492–501.
pubmed: 29114726
pmcid: 5822196
La Joie R, Bejanin A, Fagan AM, Ayakta N, Baker SL, Bourakova V, et al. Associations between [(18)F]AV1451 tau PET and CSF measures of tau pathology in a clinical sample. Neurology. 2018;90(4):e282–90.
pubmed: 29282337
pmcid: 5798657
Mattsson N, Scholl M, Strandberg O, Smith R, Palmqvist S, Insel PS, et al. (18)F-AV-1451 and CSF T-tau and P-tau as biomarkers in Alzheimer's disease. EMBO Mol Med. 2017;9(9):1212–23.
Bateman RJ, Xiong C, Benzinger TL, Fagan AM, Goate A, Fox NC, et al. Clinical and biomarker changes in dominantly inherited Alzheimer's disease. N Engl J Med. 2012;367(9):795–804.
pubmed: 22784036
pmcid: 3474597
Barthelemy NR, Li Y, Joseph-Mathurin N, Gordon BA, Hassenstab J, Benzinger TLS, et al. A soluble phosphorylated tau signature links tau, amyloid and the evolution of stages of dominantly inherited Alzheimer's disease. Nat Med. 2020;26(3):398–407.
pubmed: 32161412
pmcid: 7309367
Mattsson-Carlgren N, Andersson E, Janelidze S, Ossenkoppele R, Insel P, Strandberg O, et al. Abeta deposition is associated with increases in soluble and phosphorylated tau that precede a positive tau PET in Alzheimer's disease. Sci Adv. 2020;6(16):eaaz2387.
pubmed: 32426454
pmcid: 7159908
Toledo JB, Xie SX, Trojanowski JQ, Shaw LM. Longitudinal change in CSF tau and Abeta biomarkers for up to 48 months in ADNI. Acta Neuropathol. 2013;126(5):659–70.
pubmed: 23812320
Suarez-Calvet M, Karikari TK, Ashton NJ, Rodriguez JL, Mila-Aloma M, Gispert JD, et al. Novel tau biomarkers phosphorylated at T181, T217 or T231 rise in the initial stages of the preclinical Alzheimer’s continuum when only subtle changes in Abeta pathology are detected. EMBO Mol Med. 2020;12(12):e12921. https://doi.org/10.15252/emmm.202012921 .
Sato C, Barthelemy NR, Mawuenyega KG, Patterson BW, Gordon BA, Jockel-Balsarotti J, et al. Tau kinetics in neurons and the human central nervous system. Neuron. 2018;97(6):1284–1298 e7.
pubmed: 29566794
pmcid: 6137722
Song F, Poljak A, Valenzuela M, Mayeux R, Smythe GA, Sachdev PS. Meta-analysis of plasma amyloid-beta levels in Alzheimer's disease. J Alzheimers Dis. 2011;26(2):365–75.
pubmed: 21709378
pmcid: 5660871
Hansson O, Zetterberg H, Vanmechelen E, Vanderstichele H, Andreasson U, Londos E, et al. Evaluation of plasma Abeta(40) and Abeta(42) as predictors of conversion to Alzheimer's disease in patients with mild cognitive impairment. Neurobiol Aging. 2010;31(3):357–67.
pubmed: 18486992
Kuo YM, Emmerling MR, Lampert HC, Hempelman SR, Kokjohn TA, Woods AS, et al. High levels of circulating Abeta42 are sequestered by plasma proteins in Alzheimer's disease. Biochem Biophys Res Commun. 1999;257(3):787–91.
pubmed: 10208861
Zetterberg H, Mortberg E, Song L, Chang L, Provuncher GK, Patel PP, et al. Hypoxia due to cardiac arrest induces a time-dependent increase in serum amyloid beta levels in humans. PLoS One. 2011;6(12):e28263.
pubmed: 22194817
pmcid: 3237426
Janelidze S, Stomrud E, Palmqvist S, Zetterberg H, van Westen D, Jeromin A, et al. Plasma beta-amyloid in Alzheimer's disease and vascular disease. Sci Rep. 2016;6:26801.
pubmed: 27241045
pmcid: 4886210
Pannee J, Tornqvist U, Westerlund A, Ingelsson M, Lannfelt L, Brinkmalm G, et al. The amyloid-beta degradation pattern in plasma--a possible tool for clinical trials in Alzheimer's disease. Neurosci Lett. 2014;573:7–12.
pubmed: 24796810
Ovod V, Ramsey KN, Mawuenyega KG, Bollinger JG, Hicks T, Schneider T, et al. Amyloid beta concentrations and stable isotope labeling kinetics of human plasma specific to central nervous system amyloidosis. Alzheimers Dement. 2017;13(8):841–9.
pubmed: 28734653
pmcid: 5567785
Kaneko N, Nakamura A, Washimi Y, Kato T, Sakurai T, Arahata Y, et al. Novel plasma biomarker surrogating cerebral amyloid deposition. Proc Jpn Acad Ser B Phys Biol Sci. 2014;90(9):353–64.
pubmed: 25391320
pmcid: 4324927
Tzen KY, Yang SY, Chen TF, Cheng TW, Horng HE, Wen HP, et al. Plasma Abeta but not tau is related to brain PiB retention in early Alzheimer's disease. ACS Chem Neurosci. 2014;5(9):830–6.
pubmed: 25054847
Randall J, Mortberg E, Provuncher GK, Fournier DR, Duffy DC, Rubertsson S, et al. Tau proteins in serum predict neurological outcome after hypoxic brain injury from cardiac arrest: results of a pilot study. Resuscitation. 2013;84(3):351–6.
pubmed: 22885094
Shahim P, Tegner Y, Wilson DH, Randall J, Skillback T, Pazooki D, et al. Blood biomarkers for brain injury in concussed professional ice hockey players. JAMA Neurol. 2014;71(6):684–92.
pubmed: 24627036
Evered L, Silbert B, Scott DA, Zetterberg H, Blennow K. Association of changes in plasma neurofilament light and tau levels with anesthesia and surgery: results from the CAPACITY and ARCADIAN studies. JAMA Neurol. 2018;75(5):542–7.
pubmed: 29459944
pmcid: 5885271
Pereira JB, Westman E, Hansson O, I. Alzheimer's Disease Neuroimaging. Association between cerebrospinal fluid and plasma neurodegeneration biomarkers with brain atrophy in Alzheimer's disease. Neurobiol Aging. 2017;58:14–29.
pubmed: 28692877
Ashton NJ, Ide M, Zetterberg H, Blennow K. Salivary biomarkers for Alzheimer's disease and related disorders. Neurol Ther. 2019;8(Suppl 2):83–94.
pubmed: 31833026
pmcid: 6908535
Ashton NJ, Ide M, Scholl M, Blennow K, Lovestone S, Hye A, et al. No association of salivary total tau concentration with Alzheimer's disease. Neurobiol Aging. 2018;70:125–7.
pubmed: 30007161
Suarez-Calvet M, Karikari TK, Ashton NJ, Lantero-Rodriguez J, Mila-Aloma M, Gispert JD, et al. Novel tau biomarkers phosphorylated at T181, T217 or T231 rise in the initial stages of the preclinical Alzheimer’s continuum when only subtle changes in Ab pathology are detected. EMBO Mol Med. 2020. https://doi.org/10.15252/emmm.202012921 .
Tatebe H, Kasai T, Ohmichi T, Kishi Y, Kakeya T, Waragai M, et al. Quantification of plasma phosphorylated tau to use as a biomarker for brain Alzheimer pathology: pilot case-control studies including patients with Alzheimer's disease and down syndrome. Mol Neurodegener. 2017;12(1):63.
pubmed: 28866979
pmcid: 5582385
Mielke MM, Hagen CE, Xu J, Chai X, Vemuri P, Lowe VJ, et al. Plasma phospho-tau181 increases with Alzheimer's disease clinical severity and is associated with tau- and amyloid-positron emission tomography. Alzheimers Dement. 2018;14(8):989–97.
pubmed: 29626426
pmcid: 6097897
Palmqvist S, Insel PS, Stomrud E, Janelidze S, Zetterberg H, Brix B, et al. Cerebrospinal fluid and plasma biomarker trajectories with increasing amyloid deposition in Alzheimer's disease. EMBO Mol Med. 2019;11(12):e11170.
pubmed: 31709776
pmcid: 6895602
Karikari TK, Pascoal TA, Ashton NJ, Janelidze S, Benedet AL, Rodriguez JL, et al. Blood phosphorylated tau 181 as a biomarker for Alzheimer's disease: a diagnostic performance and prediction modelling study using data from four prospective cohorts. Lancet Neurol. 2020;19(5):422–33.
pubmed: 32333900
Janelidze S, Mattsson N, Palmqvist S, Smith R, Beach TG, Serrano GE, et al. Plasma P-tau181 in Alzheimer's disease: relationship to other biomarkers, differential diagnosis, neuropathology and longitudinal progression to Alzheimer's dementia. Nat Med. 2020;26(3):379–86.
pubmed: 32123385
Thijssen EH, La Joie R, Wolf A, Strom A, Wang P, Iaccarino L, et al. Treatment for frontotemporal lobar degeneration, diagnostic value of plasma phosphorylated tau181 in Alzheimer's disease and frontotemporal lobar degeneration. Nat Med. 2020;26(3):387–97.
pubmed: 32123386
pmcid: 7101073
Palmqvist S, Janelidze S, Quiroz YT, Zetterberg H, Lopera F, Stomrud E, et al. Discriminative accuracy of plasma phospho-tau217 for Alzheimer disease vs other neurodegenerative disorders. JAMA. 2020;324(8):772–81.
pubmed: 32722745
Ashton NJ, Pascoal TA, Karikari TK, Benedet AL, Lantero-Rodriguez J, Brinkmalm G, et al. Plasma p-tau231: a new biomarker for incipient Alzheimer’s disease pathology. Acta Neuropathol. 2021. https://doi.org/10.1007/s00401-021-02275-6 .
Startin CM, Ashton NJ, Hamburg S, Hithersay R, Wiseman FK, Mok KY, et al. Plasma biomarkers for amyloid, tau, and cytokines in down syndrome and sporadic Alzheimer's disease. Alzheimers Res Ther. 2019;11(1):26.
pubmed: 30902060
pmcid: 6429702
Palmqvist S, Janelidze S, Stomrud E, Zetterberg H, Karl J, Zink K, et al. Performance of fully automated plasma assays as screening tests for Alzheimer disease-related β-amyloid status. JAMA Neurol. 2019;76(9):1060–9. https://doi.org/10.1001/jamaneurol.2019.1632 .
Schindler SE, Bollinger JG, Ovod V, Mawuenyega KG, Li Y, Gordon BA, et al. High-precision plasma beta-amyloid 42/40 predicts current and future brain amyloidosis. Neurology. 2019;93(17):e1647–59.
pubmed: 31371569
pmcid: 6946467
Nakamura A, Kaneko N, Villemagne VL, Kato T, Doecke J, Dore V, et al. High performance plasma amyloid-beta biomarkers for Alzheimer's disease. Nature. 2018;554(7691):249–54.
pubmed: 29420472
Chiu MJ, Chen TF, Hu CJ, Yan SH, Sun Y, Liu BH, et al. Nanoparticle-based immunomagnetic assay of plasma biomarkers for differentiating dementia and prodromal states of Alzheimer's disease - a cross-validation study. Nanomedicine. 2020;28:102182.
pubmed: 32222476
Lin CH, Yang SY, Horng HE, Yang CC, Chieh JJ, Chen HH, et al. Plasma biomarkers differentiate Parkinson's disease from atypical parkinsonism syndromes. Front Aging Neurosci. 2018;10:123.
pubmed: 29755341
pmcid: 5934438
Rabinovici GD, Furst AJ, O'Neil JP, Racine CA, Mormino EC, Baker SL, et al. 11C-PIB PET imaging in Alzheimer disease and frontotemporal lobar degeneration. Neurology. 2007;68(15):1205–12.
pubmed: 17420404
Struyfs H, Niemantsverdriet E, Goossens J, Fransen E, Martin JJ, De Deyn PP, et al. Cerebrospinal fluid P-Tau181P: biomarker for improved differential dementia diagnosis. Front Neurol. 2015;6:138.
pubmed: 26136723
pmcid: 4470274
Janelidze S, Stomrud E, Smith R, Palmqvist S, Mattsson N, Airey DC, et al. Cerebrospinal fluid p-tau217 performs better than p-tau181 as a biomarker of Alzheimer's disease. Nat Commun. 2020;11(1):1683.
pubmed: 32246036
pmcid: 7125218
Karikari TK, Emersic A, Vrillon A, Lantero-Rodriguez J, Ashton NJ, Kramberger MG, et al. Head-to-head comparison of clinical performance of CSF phospho-tau T181 and T217 biomarkers for Alzheimer’s disease diagnosis. Alzheimers Dement. 2020. https://doi.org/10.1002/alz.12236 .
Barthelemy NR, Bateman RJ, Hirtz C, Marin P, Becher F, Sato C, et al. Cerebrospinal fluid phospho-tau T217 outperforms T181 as a biomarker for the differential diagnosis of Alzheimer's disease and PET amyloid-positive patient identification. Alzheimers Res Ther. 2020;12(1):26.
pubmed: 32183883
pmcid: 7079453
Hanes J, Kovac A, Kvartsberg H, Kontsekova E, Fialova L, Katina S, et al. Evaluation of a novel immunoassay to detect p-tau Thr217 in the CSF to distinguish Alzheimer disease from other dementias. Neurology. 2020. https://doi.org/10.1212/WNL.0000000000010814 .
Ashton NJ, Benedet AL, Pascoal TA, Karikari TK, Lantero-Rodriguez J, Mathotaarachchi S, et al. Cerebrospinal fluid p-tau231 as an early indicator of emerging pathology in Alzheimer’s disease. Research Square 2021. https://doi.org/10.21203/rs.3.rs-155736/v1 (PREPRINT (Version 1)).
Benussi A, Karikari TK, Ashton N, Gazzina S, Premi E, Benussi L, et al. Diagnostic and prognostic value of serum NfL and p-Tau181 in frontotemporal lobar degeneration. J Neurol Neurosurg Psychiatry. 2020;91(9):960–7.
pubmed: 32611664
Lantero Rodriguez J, Karikari TK, Suarez-Calvet M, Troakes C, King A, Emersic A, et al. 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. 2020;140(3):267–78.
pubmed: 32720099
pmcid: 7423866
Barthélemy NR, Horie K, Sato C, Bateman RJ. Blood plasma phosphorylated-tau isoforms track CNS change in Alzheimer’s disease. J Exp Med. 2020;217(11):e20200861. https://doi.org/10.1084/jem.20200861 .
O'Bryant SE, Gupta V, Henriksen K, Edwards M, Jeromin A, Lista S, et al. Guidelines for the standardization of preanalytic variables for blood-based biomarker studies in Alzheimer's disease research. Alzheimers Dement. 2015;11(5):549–60.
pubmed: 25282381
Rozga M, Bittner T, Batrla R, Karl J. Preanalytical sample handling recommendations for Alzheimer's disease plasma biomarkers. Alzheimers Dement (Amst). 2019;11:291–300.
Verberk IMW, Thijssen E, Koelewijn J, Mauroo K, Vanbrabant J, de Wilde A, et al. Combination of plasma amyloid beta(1-42/1-40) and glial fibrillary acidic protein strongly associates with cerebral amyloid pathology. Alzheimers Res Ther. 2020;12(1):118.
pubmed: 32988409
pmcid: 7523295
Verberk IMW, Slot RE, Verfaillie SCJ, Heijst H, Prins ND, van Berckel BNM, et al. Plasma amyloid as prescreener for the earliest Alzheimer pathological changes. Ann Neurol. 2018;84(5):648–58.
pubmed: 30196548
pmcid: 6282982
Vogelgsang J, Vukovich R, Wedekind D, Wiltfang J. Higher level of mismatch in APOEepsilon4 carriers for amyloid-beta peptide Alzheimer's disease biomarkers in cerebrospinal fluid. ASN Neuro. 2019;11:1759091419845524.
pubmed: 31104469
pmcid: 6535906
Lim CZJ, Zhang Y, Chen Y, Zhao H, Stephenson MC, Ho NRY, et al. Subtyping of circulating exosome-bound amyloid beta reflects brain plaque deposition. Nat Commun. 2019;10(1):1144.
pubmed: 30850633
pmcid: 6408581
Mattsson-Carlgren N, Janelidze S, Palmqvist S, Cullen N, Svenningsson AL, Strandberg O, et al. Longitudinal plasma p-tau217 is increased in early stages of Alzheimer’s disease. Brain. 2020;143(11):3234–41. https://doi.org/10.1093/brain/awaa286 .
Benussi A, Ashton NJ, Karikari TK, Gazzina S, Premi E, Benussi L, et al. Serum glial fibrillary acidic protein (GFAP) is a marker of disease severity in frontotemporal lobar degeneration. J Alzheimers Dis. 2020;77(3):1129–41.
pubmed: 32804092
Gamache J, Yun Y, Chiba-Falek O. Sex-dependent effect of APOE on Alzheimer’s disease and other age-related neurodegenerative disorders. Dis Model Mech. 2020;13(8):dmm045211. https://doi.org/10.1242/dmm.045211 .
Babapour Mofrad R, Tijms BM, Scheltens P, Barkhof F, van der Flier WM, Sikkes SAM, et al. Sex differences in CSF biomarkers vary by Alzheimer’s disease stage and APOE ε4 genotype. Neurology. 2020;27;95(17):e2378–88. https://doi.org/10.1212/WNL.0000000000010629 .
Nakamura T, Kawarabayashi T, Seino Y, Hirohata M, Nakahata N, Narita S, et al. Aging and APOE-epsilon4 are determinative factors of plasma Abeta42 levels. Ann Clin Transl Neurol. 2018;5(10):1184–91.
pubmed: 30349853
pmcid: 6186936
Knapskog AB, Eldholm RS, Braekhus A, Engedal K, Saltvedt I. Factors that influence the levels of cerebrospinal fluid biomarkers in memory clinic patients. BMC Geriatr. 2017;17(1):210.
pubmed: 28893185
pmcid: 5594466
Cullen NC, Leuzy A, Palmqvist S, Janelidze S, Stomrud E, Pesini P, et al. Individualized prognosis of cognitive decline and dementia in mild cognitive impairment based on plasma biomarker combinations. Nat Aging. 2021;1:114–23. https://doi.org/10.1038/s43587-020-00003-5 .
Karikari TK, Benedet AL, Ashton NJ, Lantero-Rodriguez J, Snellman A, Suarez-Calvet M, et al. Diagnostic performance and prediction of clinical progression of plasma phospho-tau181 in the Alzheimer’s Disease Neuroimaging Initiative. Mol Psychiatry. 2020. https://doi.org/10.1038/s41380-020-00923-z .
O'Connor A, Karikari TK, Poole T, Ashton NJ, Lantero-Rodriguez J, Khatun A, et al. Plasma phospho-tau181 in presymptomatic and symptomatic familial Alzheimer’s disease: a longitudinal cohort study. Mol Psychiatry. 2020. https://doi.org/10.1038/s41380-020-0838-x .
Pase MP, Beiser AS, Himali JJ, Satizabal CL, Aparicio HJ, DeCarli C, et al. Assessment of plasma Total tau level as a predictive biomarker for dementia and related endophenotypes. JAMA Neurol. 2019;76(5):598–606.
pubmed: 30830207
pmcid: 6515589
Kanberg N, Ashton NJ, Andersson LM, Yilmaz A, Lindh M, Nilsson S, et al. Neurochemical evidence of astrocytic and neuronal injury commonly found in COVID-19. Neurology. 2020;95(12):e1754–9.
pubmed: 32546655
Hanes J, Kovac A, Kvartsberg H, Kontsekova E, Fialova L, Katina S, et al. Evaluation of a novel immunoassay to detect p-tau Thr127 in the CSF to distinguish Alzheimer disease from other dementias. Neurology. 2020.
Janelidze S, Stomrud E, Brix B, Hansson O. Towards a unified protocol for handling of CSF before β-amyloid measurements. Alzheimers Res Ther. 2019;11(1):63. https://doi.org/10.1186/s13195-019-0517-9 .
Rajan KB, Aggarwal NT, McAninch EA, Weuve J, Barnes LL, Wilson RS, et al. Remote blood biomarkers of longitudinal cognitive outcomes in a population study. Ann Neurol. 2020.
Vanderstichele H, De Vreese K, Blennow K, Andreasen N, Sindic C, Ivanoiu A, et al. Analytical performance and clinical utility of the INNOTEST PHOSPHO-TAU181P assay for discrimination between Alzheimer’s disease and dementia with Lewy bodies. Clin Chem Lab Med. 2006;44(12):1472–80. https://doi.org/10.1515/CCLM.2006.258 .
Leitao MJ, Silva-Spinola A, Santana I, Olmedo V, Nadal A, Le Bastard N, et al. Clinical validation of the lumipulse G cerebrospinal fluid assays for routine diagnosis of Alzheimer's disease. Alzheimers Res Ther. 2019;11(1):91.
pubmed: 31759396
pmcid: 6875031
Lifke V, Kollmorgen G, Manuilova E, Oelschlaegel T, Hillringhaus L, Widmann M, et al. Elecsys((R)) total-tau and phospho-tau (181P) CSF assays: analytical performance of the novel, fully automated immunoassays for quantification of tau proteins in human cerebrospinal fluid. Clin Biochem. 2019;72:30–8.
pubmed: 31129184
Cicognola C, Brinkmalm G, Wahlgren J, Portelius E, Gobom J, Cullen NC, et al. Novel tau fragments in cerebrospinal fluid: relation to tangle pathology and cognitive decline in Alzheimer's disease. Acta Neuropathol. 2019;137(2):279–96.
pubmed: 30547227
Basurto-Islas G, Luna-Munoz J, Guillozet-Bongaarts AL, Binder LI, Mena R, Garcia-Sierra F. Accumulation of aspartic acid421- and glutamic acid391-cleaved tau in neurofibrillary tangles correlates with progression in Alzheimer disease. J Neuropathol Exp Neurol. 2008;67(5):470–83.
pubmed: 18431250
pmcid: 4699801
Fitzpatrick AWP, Falcon B, He S, Murzin AG, Murshudov G, Garringer HJ, et al. Cryo-EM structures of tau filaments from Alzheimer's disease. Nature. 2017;547(7662):185–90.
pubmed: 28678775
pmcid: 5552202
Yang CC, Chiu MJ, Chen TF, Chang HL, Liu BH, Yang SY. Assay of plasma phosphorylated tau protein (threonine 181) and total tau protein in early-stage Alzheimer's disease. J Alzheimers Dis. 2018;61(4):1323–32.
pubmed: 29376870
O'Brien RJ, Wong PC. Amyloid precursor protein processing and Alzheimer's disease. Annu Rev Neurosci. 2011;34:185–204.
pubmed: 21456963
pmcid: 3174086
Citron M, Vigo-Pelfrey C, Teplow DB, Miller C, Schenk D, Johnston J, et al. Excessive production of amyloid beta-protein by peripheral cells of symptomatic and presymptomatic patients carrying the Swedish familial Alzheimer disease mutation. Proc Natl Acad Sci U S A. 1994;91(25):11993–7.
pubmed: 7991571
pmcid: 45362
Bielinska K, Radkowski M, Grochowska M, Perlejewski K, Huc T, Jaworska K, et al. High salt intake increases plasma trimethylamine N-oxide (TMAO) concentration and produces gut dysbiosis in rats. Nutrition. 2018;54:33–9.
pubmed: 29705499
Komi R, Tanaka F, Omama S, Ishibashi Y, Tanno K, Onoda T, et al. Burden of high blood pressure as a contributing factor to stroke in the Japanese community-based diabetic population. Hypertens Res. 2018;41(7):531–8.
pubmed: 29654296
pmcid: 8075942
Strozyk D, Blennow K, White LR, Launer LJ. CSF Abeta 42 levels correlate with amyloid-neuropathology in a population-based autopsy study. Neurology. 2003;60(4):652–6.
pubmed: 12601108
Ikonomovic MD, Klunk WE, Abrahamson EE, Mathis CA, Price JC, Tsopelas ND, et al. Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer's disease. Brain. 2008;131(Pt 6):1630–45.
pubmed: 18339640
pmcid: 2408940
Clark CM, Schneider JA, Bedell BJ, Beach TG, Bilker WB, Mintun MA, et al. Use of florbetapir-PET for imaging beta-amyloid pathology. JAMA. 2011;305(3):275–83.
pubmed: 21245183
pmcid: 7041965