title: 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.
abstract: 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.
authors.affiliation: Department of Psychiatry, Hospital Universitario de Álava, Vitoria, Spain. ariadna.besgabasterra@osakidetza.net
authors.forename: A
authors.initials: A
authors.lastname: Besga
authors.forename: A
authors.initials: A
authors.lastname: Cedazo-Minguez
authors.forename: I
authors.initials: I
authors.lastname: Kåreholt
authors.forename: A
authors.initials: A
authors.lastname: Solomon
authors.forename: I
authors.initials: I
authors.lastname: Björkhem
authors.forename: B
authors.initials: B
authors.lastname: Winblad
authors.forename: V
authors.initials: V
authors.lastname: Leoni
authors.forename: B
authors.initials: B
authors.lastname: Hooshmand
authors.forename: G
authors.initials: G
authors.lastname: Spulber
authors.forename: A
authors.initials: A
authors.lastname: Gonzalez-Pinto
authors.forename: M
authors.initials: M
authors.lastname: Kivipelto
authors.forename: L O
authors.initials: LO
authors.lastname: Wahlund
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D001479:Basal Ganglia / Q000473:pathology; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002784:Cholesterol / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D005260:Female; D006801:Humans; D007328:Insulin / Q000134:cerebrospinal fluid / Q000378:metabolism*; D007810:Lanosterol / Q000097:blood / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D008569:Memory Disorders / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D007328:Insulin; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D007810:Lanosterol; C001521:lathosterol; D002784:Cholesterol