Plasma amyloid-β levels, cerebral atrophy and risk of dementia: a population-based study.

Abstract

BACKGROUND:

Plasma amyloid-β (Aβ) levels are increasingly studied as a potential accessible marker of cognitive impairment and dementia. However, it remains underexplored whether plasma Aβ levels including the novel Aβ peptide 1-38 (Aβ1-38) relate to preclinical markers of neurodegeneration and risk of dementia. We investigated the association of plasma Aβ1-38, Aβ1-40, and Aβ1-42 levels with imaging markers of neurodegeneration and risk of dementia in a prospective population-based study.

METHODS:

We analyzed plasma Aβ levels in 458 individuals from the Rotterdam Study. Brain volumes, including gray matter, white matter, and hippocampus, were computed on the basis of 1.5-T magnetic resonance imaging (MRI). Dementia and its subtypes were defined on the basis of internationally accepted criteria.

RESULTS:

A total of 458 individuals (mean age, 67.8 ± 7.7 yr; 232 [50.7%] women) with baseline MRI scans and incident dementia were included. The mean ± SD values of Aβ1-38, Aβ1-40, and Aβ1-42 (in pg/ml) were 19.4 ± 4.3, 186.1 ± 35.9, and 56.3 ± 6.2, respectively, at baseline. Lower plasma Aβ1-42 levels were associated with smaller hippocampal volume (mean difference in hippocampal volume per SD decrease in Aβ1-42 levels, - 0.13; 95% CI, - 0.23 to - 0.04; p = 0.007). After a mean follow-up of 14.8 years (SD, 4.9; range, 4.1-23.5 yr), 79 persons developed dementia, 64 of whom were diagnosed with Alzheimer's disease (AD). Lower levels of Aβ1-38 and Aβ1-42 were associated with increased risk of dementia, specifically AD (HR for AD per SD decrease in Aβ1-38 levels, 1.39; 95% CI, 1.00-2.16; HR for AD per SD decrease in Aβ1-42 levels, 1.35; 95% CI, 1.05-1.75) after adjustment for age, sex, education, cardiovascular risk factors, apolipoprotein E ε4 allele carrier status, and other Aβ isoforms.

CONCLUSIONS:

Our results show that lower plasma Aβ levels were associated with risk of dementia and incident AD. Moreover, lower plasma Aβ1-42 levels were related to smaller hippocampal volume. These results suggest that plasma Aβ1-38 and Aβ1-42 maybe useful biomarkers for identification of individuals at risk of dementia.

• Authors: Saima Hilal, Frank J Wolters, Marcel M Verbeek, Hugo Vanderstichele, M Kamran Ikram, Erik Stoops, M Arfan Ikram, Meike W Vernooij
• Journal: Alzheimer's research & therapy (Alzheimers Res Ther) Vol. 10 Issue 1 Pg. 63 (06 30 2018) ISSN: 1758-9193 [Electronic] England
• PMID: 29960604 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides
• Apolipoprotein E4
• apolipoprotein E4 (Freiburg)

Topics

• Aged
• Amyloid beta-Peptides (blood)
• Apolipoprotein E4 (genetics)
• Atrophy (blood, diagnostic imaging)
• Brain (diagnostic imaging)
• Cerebral Cortex (pathology)
• Cohort Studies
• Community Health Planning
• Dementia (blood, diagnostic imaging, epidemiology, genetics)
• Female
• Humans
• Imaging, Three-Dimensional
• Magnetic Resonance Imaging
• Male
• Mental Status and Dementia Tests
• Middle Aged