Clinical Significance of the Plasma Biomarker Panels in Amyloid-Negative and Tau PET-Positive Amnestic Patients: Comparisons with Alzheimer's Disease and Unimpaired Cognitive Controls.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Alzheimer Disease*/blood ; Alzheimer Disease*/diagnostic imaging ; Alzheimer Disease*/diagnosis ; tau Proteins*/blood ; Biomarkers*/blood ; Positron-Emission Tomography*/methods ; Amyloid beta-Peptides*/blood; Humans ; Male ; Female ; Aged ; Middle Aged ; Cognition ; Hippocampus/diagnostic imaging ; Hippocampus/pathology ; Hippocampus/metabolism ; Neurofilament Proteins/blood ; Aged, 80 and over ; Amnesia/blood ; Amnesia/diagnostic imaging ; Amnesia/diagnosis ; ROC Curve ; Clinical Relevance

The purpose of this study was to investigate whether plasma biomarkers can help to diagnose, differentiate from Alzheimer disease (AD), and stage cognitive performance in patients with positron emission tomography (PET)-confirmed primary age-related tauopathy, termed tau-first cognitive proteinopathy (TCP) in this study. In this multi-center study, we enrolled 285 subjects with young-onset AD (YOAD; n = 55), late-onset AD (LOAD; n = 96), TCP ( n = 44), and cognitively unimpaired controls (CTL; n = 90) and analyzed plasma Aβ42/Aβ40, pTau181, neurofilament light (NFL), and total-tau using single-molecule assays. Amyloid and tau centiloids reflected pathological burden, and hippocampal volume reflected structural integrity. Receiver operating characteristic curves and areas under the curves (AUCs) were used to determine the diagnostic accuracy of plasma biomarkers compared to hippocampal volume and amyloid and tau centiloids. The Mini-Mental State Examination score (MMSE) served as the major cognitive outcome. Logistic stepwise regression was used to assess the overall diagnostic accuracy, combining fluid and structural biomarkers and a stepwise linear regression model for the significant variables for MMSE. For TCP, tau centiloid reached the highest AUC for diagnosis (0.79), while pTau181 could differentiate TCP from YOAD (accuracy 0.775) and LOAD (accuracy 0.806). NFL reflected the clinical dementia rating in TCP, while pTau181 (rho = 0.3487, p = 0.03) and Aβ42/Aβ40 (rho = -0.36, p = 0.02) were significantly correlated with tau centiloid. Hippocampal volume (unstandardized β = 4.99, p = 0.01) outperformed all of the fluid biomarkers in predicting MMSE scores in the TCP group. Our results support the superiority of tau PET to diagnose TCP, pTau181 to differentiate TCP from YOAD or LOAD, and NFL for functional staging.

Mov Disord. 2017 Jun;32(6):853-864. (PMID: 28467028)
Int J Mol Sci. 2022 Nov 23;23(23):. (PMID: 36498962)
Neurology. 2008 Aug 26;71(9):670-6. (PMID: 18725592)
Brain. 2023 Aug 1;146(8):3192-3205. (PMID: 37082959)
JAMA Neurol. 2022 Dec 1;79(12):1250-1259. (PMID: 36251300)
Acta Neurol Taiwan. 2012 Dec;21(4):180-9. (PMID: 23329550)
Acta Neuropathol. 2021 May;141(5):697-708. (PMID: 33723967)
J Neuropathol Exp Neurol. 2016 Apr;75(4):316-25. (PMID: 26979082)
Nat Med. 2022 Dec;28(12):2555-2562. (PMID: 36456833)
Alzheimers Dement. 2022 Feb;18(2):240-250. (PMID: 34310015)
Neuron. 2021 Jan 6;109(1):42-58.e8. (PMID: 33125873)
Nat Rev Neurol. 2020 May;16(5):265-284. (PMID: 32322100)
J Pathol Transl Med. 2019 May;53(3):159-163. (PMID: 30887795)
Alzheimers Dement. 2018 Apr;14(4):535-562. (PMID: 29653606)
J Nucl Med. 2022 Jan;63(1):108-116. (PMID: 33863821)
Alzheimers Dement. 2022 Jun;18(6):1141-1154. (PMID: 34494715)
Mov Disord. 2021 Oct;36(10):2314-2323. (PMID: 34089275)
J Neuropathol Exp Neurol. 2019 Mar 1;78(3):219-228. (PMID: 30715383)
Lancet Neurol. 2016 Jun;15(7):673-684. (PMID: 27068280)
Alzheimers Dement. 2017 Sep;13(9):1048-1053. (PMID: 28322204)
Arch Neurol. 1999 Jan;56(1):33-9. (PMID: 9923759)
J Alzheimers Dis. 2015;43(1):183-91. (PMID: 25079805)
JAMA Neurol. 2021 Sep 1;78(9):1108-1117. (PMID: 34309632)
Acta Neuropathol. 2020 Sep;140(3):267-278. (PMID: 32720099)
Brain. 2023 Aug 1;146(8):3106-3109. (PMID: 37327374)
Lancet Neurol. 2021 Jun;20(6):484-496. (PMID: 33933186)
Alzheimers Dement. 2019 Oct;15(10):1286-1295. (PMID: 31495603)
Alzheimers Dement. 2022 Jan;18(1):77-87. (PMID: 34057802)
Lancet Neurol. 2022 Jan;21(1):66-77. (PMID: 34838239)
Acta Neuropathol. 2023 Jul;146(1):1-11. (PMID: 37031430)
Neuroimage. 2012 Jul 16;61(4):1402-18. (PMID: 22430496)
Nat Rev Neurol. 2022 Jul;18(7):400-418. (PMID: 35585226)
Neurobiol Aging. 2022 Jan;109:125-134. (PMID: 34715443)
Neurology. 2013 Jan 29;80(5):496-503. (PMID: 23359374)
J Int Neuropsychol Soc. 2010 Mar;16(2):244-51. (PMID: 20003579)
Neuroimage. 2018 May 1;171:6-14. (PMID: 29288131)
Acta Neuropathol. 2015 May;129(5):749-56. (PMID: 25628035)
Nat Neurosci. 2020 Oct;23(10):1183-1193. (PMID: 32778792)
Alzheimers Dement. 2019 Jun;15(6):799-806. (PMID: 31056344)
Nat Rev Neurol. 2016 Feb;12(2):117-24. (PMID: 26782335)
JAMA Neurol. 2019 Sep 01;76(9):1035-1048. (PMID: 31206160)
JAMA. 2023 Aug 8;330(6):512-527. (PMID: 37459141)
Acta Neuropathol Commun. 2019 Dec 9;7(1):204. (PMID: 31818331)
Front Aging Neurosci. 2021 Dec 17;13:721217. (PMID: 34975449)
Alzheimers Dement. 2021 Aug;17(8):1353-1364. (PMID: 33580742)
Brain. 2020 Feb 1;143(2):611-621. (PMID: 31942622)
Nat Commun. 2021 Jun 7;12(1):3400. (PMID: 34099648)
Nat Med. 2020 Mar;26(3):379-386. (PMID: 32123385)
Nat Rev Neurosci. 2020 Jan;21(1):21-35. (PMID: 31780819)
Alzheimers Res Ther. 2022 Feb 1;14(1):20. (PMID: 35105351)
Lab Invest. 2019 Jul;99(7):1049-1055. (PMID: 30710118)
Alzheimers Dement. 2019 Jan;15(1):8-16. (PMID: 30465754)
Acta Neuropathol. 2014 Dec;128(6):755-66. (PMID: 25348064)
Brain Commun. 2020;2(1):fcz046. (PMID: 32051933)
J Neuropsychiatry Clin Neurosci. 2002 Fall;14(4):424-9. (PMID: 12426410)
Brain Pathol. 2021 Mar;31(2):381-384. (PMID: 33147361)
EBioMedicine. 2022 Feb;76:103836. (PMID: 35158308)
Eur J Nucl Med Mol Imaging. 2021 Jul;48(7):2140-2156. (PMID: 33677733)
Neuron. 2008 Nov 26;60(4):534-42. (PMID: 19038212)

CORPG8N0041, CMRPG8J0524, CMRPG8J0843, CMRPG8K1533 Chang Gung Memorial Hospital; NSTC 112-2321-B-182A-004 National Science and Technology Council, Taiwan

Keywords: florzolotau; pTau181; primary age-related tauopathy; tau first cognitive tauopathy

0 (tau Proteins)
0 (Biomarkers)
0 (Amyloid beta-Peptides)
0 (Neurofilament Proteins)
0 (neurofilament protein L)

Date Created: 20240619 Date Completed: 20240619 Latest Revision: 20240620

20240620

PMC11171590

10.3390/ijms25115607

38891795