Differences in brain cholesterol metabolism and insulin in two subgroups of patients with different CSF biomarkers but similar white matter lesions suggest different pathogenic mechanisms

• Published in: Neuroscience letters Vol. 510; no. 2; pp. 121 - 126
• Main Authors: Besga, A., Cedazo-Minguez, A., Kåreholt, I., Solomon, A., Björkhem, I., Winblad, B., Leoni, V., Hooshmand, B., Spulber, G., Gonzalez-Pinto, A., Kivipelto, M., Wahlund, L.O.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 29.02.2012
• Subjects: A beta 42; Aged; Alzheimer disease; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Amyloid beta-Peptides - cerebrospinal fluid; Aβ42; Basal Ganglia - pathology; Biomarkers - cerebrospinal fluid; Brain - metabolism; Brain - pathology; Cholesterol; Cholesterol - blood; Cholesterol - cerebrospinal fluid; Cholesterol - metabolism; Female; Humans; Hyperintensities; Insulin - cerebrospinal fluid; Insulin - metabolism; Lanosterol - blood; Lanosterol - metabolism; Magnetic Resonance Imaging; Male; Medicin och hälsovetenskap; Memory Disorders - metabolism; Memory Disorders - pathology; Middle Aged; Oxysterols; Peptide Fragments - cerebrospinal fluid; Tau; tau Proteins - cerebrospinal fluid; Tau; Hyperintensities; Aβ42; Alzheimer disease; Cholesterol; Oxysterols
• ISSN: 0304-3940; 1872-7972; 1872-7972
• DOI: 10.1016/j.neulet.2012.01.017

► This study investigates the pathogenesis of WMHs in elderly with memory complaints. ► Combined quantitative metabolic analysis and brain MRIs. ► The median of the combination of CSF Aβ42 and T-tau levels defines group belonging. ► The two study groups have similar appearance on FLAIR images. ► Correlation between WMHs and cholesterol–insulin metabolism differ in the groups. Investigate possible associations of white matter hyperintensities (WMHs) with the metabolism of cholesterol and insulin in two subgroups of patients with memory complaints and different CSF Aβ42 and CSF tau levels. 59 patients from the memory clinic at Karolinska Hospital were included. Degree of WMHs was rated using the ARWMC scale and the following biomarkers were measured in CSF and plasma: insulin, cholesterol, lanosterol, lathosterol, and oxidized cholesterol metabolites. The WMHs in CSF control-like group correlated with increased brain cholesterol synthesis and reduced efflux of oxysterols and insulin in CSF. In the CSF AD-like group, the WMHs correlated with increased peripheral cholesterol metabolism. Despite having similar appearance on FLAIR images, the pathogenic mechanisms of WMHS are likely to be different in the two groups investigated.