Journal
JOURNAL OF ALZHEIMERS DISEASE
Volume 27, Issue 3, Pages 665-676Publisher
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
- Swedish Brain Power
- Swedish Research Council
- Alzheimer's Association
- cNEUPRO
- Royal Swedish Academy of Sciences
- Sahlgrenska University Hospital
- Inga-Britt and Arne Lundberg Research Foundation
- Goteborg Medical Society
- Swedish Medical Society
- Demensfonden
- Stiftelsen Gamla Tjanarinnor
- Gun och Bertil Stohnes stiftelse
- Adlerbert Research Foundation
- 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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