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Sci Rep. 2016 Feb 9;6:20709. doi: 10.1038/srep20709.

Cerebral white matter lesions - associations with Aβ isoforms and amyloid PET.

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Diagnostic Radiology, Department of Clinical Sciences Lund, Lund University.
Imaging and Function, Skåne University Health Care, Lund Sweden.
Psychiatry, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.
Division of Psychiatry Skåne, Lund, Sweden.
Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.
Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Sweden.
Memory Clinic, Skåne University Health Care, Malmö, Sweden.
Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London WC1N 3BG, United Kingdom.


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.

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