title: Cerebrospinal fluid matrix metalloproteinases and tissue inhibitor of metalloproteinases in combination with subcortical and cortical biomarkers in vascular dementia and Alzheimer's disease.
abstract: Alzheimer's disease (AD) and vascular dementia (VaD) are intertwined by mixed dementia (MD) harboring varying degrees of AD pathology in combination with cerebrovascular disease. The aim was to assess whether there is a difference in the cerebrospinal fluid (CSF) profile, of selected proteins, between patients with VaD and MD with subcortical vascular disease (SVD), AD, and healthy controls that could contribute in the separation of the groups. The study included 30 controls, 26 SVD patients (9 VaD and 17 MD) and 30 AD patients. The protein panel included total tau (T-tau), hyperphosphorylated tau 181 (P-tau(181)), amyloid β 1-42 (Aβ(1-42)), neurofilament light (NF-L), myelin basic protein (MBP), heart fatty acid binding protein (H-FABP), matrix metalloproteinases (MMP-1, -2, -3, -9, and -10), and tissue inhibitors of metalloproteinases (TIMP-1 and -2). Immunochemical methods were utilized for quantification of the proteins in CSF and data analysis was performed with a multivariate discriminant algorithm. The concentrations of MBP, TIMP-1, P-tau(181), NF-L, T-tau, MMP-9, Aβ(1-42), and MMP-2 contributed the most to the separation between SVD and AD, with a sensitivity of 89% and a specificity of 90% (AUC = 0.92). MBP and NF-L performed the best in discriminating SVD from controls, while T-tau and Aβ(1-42) contributed the most in segregating AD from controls. The CSF biomarkers reflecting AD pathology (T-tau, P-tau(181), and Aβ(1-42)), white matter lesions (NF-L and MBP) and matrix remodeling (MMP-9 and TIMP-1) perform well in differentiating between SVD and AD patients.
authors.affiliation: Institute of Neuroscience and physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Bjerke
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.forename: Åke
authors.initials: Å
authors.lastname: Edman
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.forename: Anders
authors.initials: A
authors.lastname: Wallin
authors.forename: Ulf
authors.initials: U
authors.lastname: Andreasson
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000201:enzymology; D015415:Biomarkers / Q000134:cerebrospinal fluid; D002540:Cerebral Cortex / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D015140:Dementia, Vascular / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000201:enzymology; D005260:Female; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000134:cerebrospinal fluid*; D008875:Middle Aged; D004676:Myelin Basic Protein / Q000134:cerebrospinal fluid; D016900:Neurofilament Proteins / Q000134:cerebrospinal fluid; D010766:Phosphorylation; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000134:cerebrospinal fluid*; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D015415:Biomarkers; C499048:MBP protein, human; D004676:Myelin Basic Protein; D016900:Neurofilament Proteins; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; C044882:neurofilament protein L; D016875:tau Proteins; D020780:Matrix Metalloproteinase 9