Cerebral white matter lesions – associations with Aβ isoforms and amyloid PET
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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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CSF+/PET− subjects are not all early Aβ accumulators since this state also can be caused by CSF analytical factors, failed PET scans, and medical conditions other than AD.
“Nonetheless, we acknowledge that CSF+/PET− subjects are not all early Aβ accumulators since this state also can be caused by CSF analytical factors, failed PET scans, and medical conditions other than AD36–38.”
From Earliest accumulation of β-amyloid occurs within the default-mode network and concurrently affects brain connectivity (2017) · cites this paper as [38]
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- Authors
- van Westen, D., Lindqvist, D., Blennow, K., Minthon, L., Nägga, K., Stomrud, E., Zetterberg, H., & Hansson, O.
- Affiliations
- Lund University (SE)
- University of Gothenburg (SE)
- National Hospital for Neurology and Neurosurgery (GB)
- Venue
- Scientific Reports
- Published
- 2016-02-09
- Volume
- 6
- Issue
- 1
- Pages
- 20709-20709
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC4746584
- OpenAlex
- W2394753565
- Cited by
- 66
- References
- 64
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 8 · 2023: 8 · 2022: 6 · 2021: 7 · 2020: 7 · 2019: 11 · 2018: 7 · 2017: 3 · 2016: 3
- FWCI
- 7.11
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- Torsten Söderbergs Stiftelse
- Stiftelsen för Gamla Tjänarinnor
- Australian Government
- Royal Swedish Academy of Sciences
- Crafoordska Stiftelsen
- Lunds Universitet
- Knut och Alice Wallenbergs Stiftelse
- Vetenskapsrådet
- Skånes universitetssjukhus
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Neurology › Cerebrovascular and genetic disorders
- Keywords
- cerebral white matter lesions, cerebral small vessel disease, amyloid-beta isoforms, cerebrospinal fluid amyloid-beta, Aβ40, amyloid-beta 42, amyloid PET, 18F-flutemetamol, lacunes, Alzheimer's disease, temporal lobe, amyloid-beta clearance
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Aniline Compounds, Female, Humans, Male, Middle Aged, Temporal Lobe, Amyloid beta-Peptides, Protein Isoforms, Positron-Emission Tomography, Benzothiazoles, White Matter
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