title: Cerebral white matter lesions - associations with Aβ isoforms and amyloid PET.
abstract: Small vessel disease (SVD) and amyloid deposition may promote each other, with a potential association between SVD and altered production or clearance of β-amyloid (Aβ) affecting its cleavage products. We investigated the relationship between SVD, multiple isoforms of Aβ in cerebrospinal fluid (CSF) and cortical Aβ in 831 subjects with cognitive performance ranging from normal to Alzheimer's disease (AD) (the Swedish BioFINDER study). SVD was estimated as white matter lesions (WML) and lacunes. 18F-flutemetamol PET was performed in 321 subjects. Lower CSF levels of Aβ38 and Aβ40 were consistently associated with increased WML in all subgroups, while lower levels of CSF Aβ42 were associated with WML mainly in AD. CSF Aβ38 and Aβ40 were associated with regional WML in all regions, while CSF Aβ42 was associated with temporal WML only. A composite measure of 18F-flutemetamol uptake was not associated with WML, and regional 18F-flutemetamol uptake only with temporal WML. Lacunes were not associated with Aβ isoforms nor 18F-flutemetamol uptake. Our results suggest that WML may be associated with alterations in the production or clearance of Aβ species, particularly of Aβ38 and Aβ40. However, in AD cases, Aβ42 pathology might be associated with WML, especially in the temporal lobe.
authors: Diagnostic Radiology, Department of Clinical Sciences Lund, Lund University.|Imaging and Function, Skåne University Health Care, Lund Sweden.
authors: Danielle
authors: D
authors: van Westen
authors: Psychiatry, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.|Division of Psychiatry Skåne, Lund, Sweden.
authors: Daniel
authors: D
authors: Lindqvist
authors: Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.
authors: Kaj
authors: K
authors: Blennow
authors: Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Sweden.|Memory Clinic, Skåne University Health Care, Malmö, Sweden.
authors: Lennart
authors: L
authors: Minthon
authors: Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Sweden.|Memory Clinic, Skåne University Health Care, Malmö, Sweden.
authors: Katarina
authors: K
authors: Nägga
authors: Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Sweden.|Memory Clinic, Skåne University Health Care, Malmö, Sweden.
authors: Erik
authors: E
authors: Stomrud
authors: Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.|Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London WC1N 3BG, United Kingdom.
authors: Henrik
authors: H
authors: Zetterberg
authors: Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Sweden.|Memory Clinic, Skåne University Health Care, Malmö, Sweden.
authors: Oskar
authors: O
authors: Hansson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000000981:diagnostic imaging; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D000814:Aniline Compounds / Q000008:administration & dosage; D052160:Benzothiazoles / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D020033:Protein Isoforms / Q000134:cerebrospinal fluid; D013702:Temporal Lobe / Q000000981:diagnostic imaging / Q000378:metabolism; D066127:White Matter / Q000000981:diagnostic imaging / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D052160:Benzothiazoles; D020033:Protein Isoforms; C581552:flutemetamol