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: Danielle van Westen, Daniel Lindqvist, Kaj Blennow, Lennart Minthon, Katarina Nägga, Erik Stomrud, Henrik Zetterberg, Oskar Hansson
• Journal: Scientific reports (Sci Rep) Vol. 6 Pg. 20709 (Feb 09 2016) ISSN: 2045-2322 [Electronic] England
• PMID: 26856756 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides
• Aniline Compounds
• Benzothiazoles
• Protein Isoforms
• flutemetamol

Topics

• Aged
• Aged, 80 and over
• Alzheimer Disease (cerebrospinal fluid, diagnostic imaging)
• Amyloid beta-Peptides (cerebrospinal fluid)
• Aniline Compounds (administration & dosage)
• Benzothiazoles (administration & dosage)
• Female
• Humans
• Male
• Middle Aged
• Positron-Emission Tomography
• Protein Isoforms (cerebrospinal fluid)
• Temporal Lobe (diagnostic imaging, metabolism)
• White Matter (diagnostic imaging, metabolism)