Blood biomarkers in mild cognitive impairment patients: Relationship between analytes and progression to Alzheimer disease dementia

被引:19
作者
Silva-Spinola, Anuschka [1 ,2 ,3 ]
Lima, Marisa [1 ,4 ,5 ]
Leitao, Maria Joao [1 ]
Bernardes, Catarina [4 ]
Duraes, Joao [1 ,3 ,4 ]
Duro, Diana [1 ,4 ]
Tabuas-Pereira, Miguel [1 ,3 ,4 ]
Santana, Isabel [1 ,3 ,4 ]
Baldeiras, Ines [1 ,3 ]
机构
[1] Univ Coimbra, Ctr Innovat Biomed & Biotechnol, Coimbra, Portugal
[2] Univ Coimbra, Ctr Informat & Syst, Dept Informat Engn, Coimbra, Portugal
[3] Univ Coimbra, Fac Med, Coimbra, Portugal
[4] Ctr Hosp & Univ Coimbra, Neurol Dept, Coimbra, Portugal
[5] Univ Coimbra, Fac Psychol & Educ Sci, Ctr Res Neuropsychol & Cognit Behav Intervent, Coimbra, Portugal
关键词
Alzheimer disease; biomarkers; blood-based; cognition; ASSOCIATION WORKGROUPS; DIAGNOSTIC GUIDELINES; NATIONAL INSTITUTE; RECOMMENDATIONS;
D O I
10.1111/ene.15762
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Background and purpose: Blood-based biomarkers are promising tools for the diagnosis of Alzheimer disease (AD) at prodromal stages (mild cognitive impairment [MCI]) and are hoped to be implemented as screening tools for patients with cognitive complaints. In this work, we evaluated the potential of peripheral neurological biomarkers to predict progression to AD dementia and the relation between blood and cerebrospinal fluid (CSF) AD markers in MCI patients referred from a general neurological department. Methods: A group of 106 MCI patients followed at the Neurology Department of Coimbra University Hospital was included. Data regarding baseline neuropsychological evaluation, CSF levels of amyloid beta 42 (A beta 42), A beta 40, total tau (t-Tau), and phosphorylated tau 181 (p-Tau181) were available for all the patients. A beta 42, A beta 40, t-Tau, p-Tau181, glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) levels were determined in baseline stored serum and plasma samples by commercial SiMoA (Single Molecule Array) assays. Progression from MCI to AD dementia was assessed at follow-up (mean = 5.8 +/- 3.4 years). Results: At baseline, blood markers NfL, GFAP, and p-Tau181 were significantly increased in patients who progressed to AD at follow-up (p < 0.001). In contrast, plasma A beta 42/40 ratio and t-Tau showed no significant differences between groups. NfL, GFAP, and p-Tau181 demonstrated good diagnostic accuracy to identify progression to AD dementia (area under the curve [AUC] = 0.81, 0.80, and 0.76, respectively), which improved when combined (AUC = 0.89). GFAP and p-Tau181 were correlated with CSF Ab42. Association of p-Tau181 with NfL was mediated by GFAP, with a significant indirect association of 88% of the total effect. Conclusions Our findings highlight the potential of combining blood-based GFAP, NfL, and p-Tau181 to be applied as a prognostic tool in MCI.
引用
收藏
页码:1565 / 1573
页数:9
相关论文
共 45 条
[1]   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 [J].
Albert, Marilyn S. ;
DeKosky, Steven T. ;
Dickson, Dennis ;
Dubois, Bruno ;
Feldman, Howard H. ;
Fox, Nick C. ;
Gamst, Anthony ;
Holtzman, David M. ;
Jagust, William J. ;
Petersen, Ronald C. ;
Snyder, Peter J. ;
Carrillo, Maria C. ;
Thies, Bill ;
Phelps, Creighton H. .
ALZHEIMERS & DEMENTIA, 2011, 7 (03) :270-279
[2]   Addition of the Aβ42/40 ratio to the cerebrospinal fluid biomarker profile increases the predictive value for underlying Alzheimer's disease dementia in mild cognitive impairment [J].
Baldeiras, Ines ;
Santana, Isabel ;
Leitao, Maria Joao ;
Gens, Helena ;
Pascoal, Rui ;
Tabuas-Pereira, Miguel ;
Beato-Coelho, Jose ;
Duro, Diana ;
Almeida, Maria Rosario ;
Oliveira, Catarina Resende .
ALZHEIMERS RESEARCH & THERAPY, 2018, 10
[3]   Blood neurofilament light: a critical review of its application to neurologic disease [J].
Barro, Christian ;
Chitnis, Tanuja ;
Weiner, Howard L. .
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY, 2020, 7 (12) :2508-2523
[4]   Clinical and analytical comparison of six Simoa assays for plasma P-tau isoforms P-tau181, P-tau217, and P-tau231 [J].
Bayoumy, Sherif ;
Verberk, Inge M. W. ;
den Dulk, Ben ;
Hussainali, Zulaiga ;
Zwan, Marissa ;
van der Flier, Wiesje M. ;
Ashton, Nicholas J. ;
Zetterberg, Henrik ;
Blennow, Kaj ;
Vanbrabant, Jeroen ;
Stoops, Erik ;
Vanmechelen, Eugeen ;
Dage, Jeffrey L. ;
Teunissen, Charlotte E. .
ALZHEIMERS RESEARCH & THERAPY, 2021, 13 (01)
[5]   The accuracy and robustness of plasma biomarker models for amyloid PET positivity [J].
Benedet, Andrea L. ;
Brum, Wagner S. ;
Hansson, Oskar ;
Initiative, Alzheimer's Disease Neuroimaging ;
Karikari, Thomas K. ;
Zimmer, Eduardo R. ;
Zetterberg, Henrik ;
Blennow, Kaj ;
Ashton, Nicholas J. .
ALZHEIMERS RESEARCH & THERAPY, 2022, 14 (01)
[6]   Differences Between Plasma and Cerebrospinal Fluid Glial Fibrillary Acidic Protein Levels Across the Alzheimer Disease Continuum [J].
Benedet, Andrea L. ;
Mila-Aloma, Marta ;
Vrillon, Agathe ;
Ashton, Nicholas J. ;
Pascoal, Tharick A. ;
Lussier, Firoza ;
Karikari, Thomas K. ;
Hourregue, Claire ;
Cognat, Emmanuel ;
Dumurgier, Julien ;
Stevenson, Jenna ;
Rahmouni, Nesrine ;
Pallen, Vanessa ;
Poltronetti, Nina M. ;
Salvado, Gemma ;
Shekari, Mahnaz ;
Operto, Gregory ;
Gispert, Juan Domingo ;
Minguillon, Carolina ;
Fauria, Karine ;
Kollmorgen, Gwendlyn ;
Suridjan, Ivonne ;
Zimmer, Eduardo R. ;
Zetterberg, Henrik ;
Molinuevo, Jose Luis ;
Paquet, Claire ;
Rosa-Neto, Pedro ;
Blennow, Kaj ;
Suarez-Calvet, Marc .
JAMA NEUROLOGY, 2021, 78 (12) :1471-1483
[7]   Trail Making Test: Regression-based Norms for the Portuguese Population [J].
Cavaco, Sara ;
Goncalves, Alexandra ;
Pinto, Claudia ;
Almeida, Eduarda ;
Gomes, Filomena ;
Moreira, Ines ;
Fernandes, Joana ;
Teixeira-Pinto, Armando .
ARCHIVES OF CLINICAL NEUROPSYCHOLOGY, 2013, 28 (02) :189-198
[8]   Plasma glial fibrillary acidic protein is elevated in cognitively normal older adults at risk of Alzheimer's disease [J].
Chatterjee, Pratishtha ;
Pedrini, Steve ;
Stoops, Erik ;
Goozee, Kathryn ;
Villemagne, Victor L. ;
Asih, Prita R. ;
Verberk, Inge M. W. ;
Dave, Preeti ;
Taddei, Kevin ;
Sohrabi, Hamid R. ;
Zetterberg, Henrik ;
Blennow, Kaj ;
Teunissen, Charlotte E. ;
Vanderstichele, Hugo M. ;
Martins, Ralph N. .
TRANSLATIONAL PSYCHIATRY, 2021, 11 (01)
[9]   Plasma neurofilament light and phosphorylated tau 181 as biomarkers of Alzheimer's disease pathology and clinical disease progression [J].
Clark, Christopher ;
Lewczuk, Piotr ;
Kornhuber, Johannes ;
Richiardi, Jonas ;
Marechal, Benedicte ;
Karikari, Thomas K. ;
Blennow, Kaj ;
Zetterberg, Henrik ;
Popp, Julius .
ALZHEIMERS RESEARCH & THERAPY, 2021, 13 (01)
[10]  
del Campo M, 2012, BIOMARK MED, V6, P419, DOI [10.2217/BMM.12.46, 10.2217/bmm.12.46]