White Matter Hyperintensities Are No Major Confounder for Alzheimer's Disease Cerebrospinal Fluid Biomarkers

Background: The cerebrospinal fluid (CSF) biomarkers amyloid-beta 1-42 (A beta(42)), total and phosphorylated tau (t-tau, p-tau) are increasingly used to assist in the clinical diagnosis of Alzheimer's disease (AD). However, CSF biomarker levels can be affected by confounding factors. Objective...

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Detalles Bibliográficos
Autores: van Doorn, LJCV, Ghafoorian, M, van Leijsen, EMC, Claassen, JAHR, Arighi, A, Bozzali, M, Cannas, J, Cavedo, E, Eusebi, P, Farotti, L, Fenoglio, C, Fortea, J, Frisoni, GB, Galimberti, D, Greco, V, Herukka, SK, Liu, YW, Lleo, A, de Mendonca, A, Nobili, FM, Parnetti, L, Picco, A, Pikkarainen, M, Salvadori, N, Scarpini, E, Soininen, H, Tarducci, R, Urbani, A, Vilaplana, E, Meulenbroek, O, Platel, B, Verbeek, MM, Kuiperij, HB
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
Repositorio:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
OAI Identifier:oai:iibsantpau.fundanetsuite.com:p4178
Acceso en línea:https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=4178
http://ddd.uab.cat/record/238669
Access Level:acceso abierto
Palabra clave:Alzheimer's disease
amyloid
biomarkers
cerebrospinal fluid
magnetic resonance imaging
tau proteins
white matter hyperintensities
white matter lesions
Descripción
Sumario:Background: The cerebrospinal fluid (CSF) biomarkers amyloid-beta 1-42 (A beta(42)), total and phosphorylated tau (t-tau, p-tau) are increasingly used to assist in the clinical diagnosis of Alzheimer's disease (AD). However, CSF biomarker levels can be affected by confounding factors. Objective: To investigate the association of white matter hyperintensities (WMHs) present in the brain with AD CSF biomarker levels. Methods: We included CSF biomarker and magnetic resonance imaging (MRI) data of 172 subjects (52 controls, 72 mild cognitive impairment (MCI), and 48 AD patients) from 9 European Memory Clinics. A computer aided detection system for standardized automated segmentation of WMHs was used on MRI scans to determine WMH volumes. Association of WMH volume with AD CSF biomarkers was determined using linear regression analysis. Results: A small, negative association of CSF A beta(42), but not p-tau and t-tau, levels with WMH volume was observed in the AD (r(2) = 0.084, p = 0.046), but not the MCI and control groups, which was slightly increased when including the distance of WMHs to the ventricles in the analysis (r(2) = 0.105, p = 0.025). Three global patterns of WMH distribution, either with 1) a low, 2) a peak close to the ventricles, or 3) a high, broadly-distributed WMH volume could be observed in brains of subjects in each diagnostic group. Conclusion: Despite an association of WMH volume with CSF A beta(42) levels in AD patients, the occurrence of WMHs is not accompanied by excess release of cellular proteins in the CSF, suggesting that WMHs are no major confounder for AD CSF biomarker assessment.

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