4.5 Article

Cerebrospinal Fluid Matrix Metalloproteinases and Tissue Inhibitor of Metalloproteinases in Combination with Subcortical and Cortical Biomarkers in Vascular Dementia and Alzheimer's Disease

Journal

JOURNAL OF ALZHEIMERS DISEASE
Volume 27, Issue 3, Pages 665-676

Publisher

IOS PRESS
DOI: 10.3233/JAD-2011-110566

Keywords

Alzheimer's disease; amyloid-beta; biomarkers; cerebrospinal fluid; matrix metalloproteinases; myelin basic protein; neurofilament light; tau; vascular dementia

Categories

Funding

  1. Swedish Brain Power
  2. Swedish Research Council
  3. Alzheimer's Association
  4. cNEUPRO
  5. Royal Swedish Academy of Sciences
  6. Sahlgrenska University Hospital
  7. Inga-Britt and Arne Lundberg Research Foundation
  8. Goteborg Medical Society
  9. Swedish Medical Society
  10. Demensfonden
  11. Stiftelsen Gamla Tjanarinnor
  12. Gun och Bertil Stohnes stiftelse
  13. Adlerbert Research Foundation
  14. Alzheimer Foundation, Sweden

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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-tau181), amyloid beta 1-42 (A beta(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, A beta(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 A beta(1-42) contributed the most in segregating AD from controls. The CSF biomarkers reflecting AD pathology (T-tau, P-tau181, and A beta(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.

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