Association of β-Amyloid, Microglial Activation, Cortical Thickness, and Metabolism in Older Adults Without Dementia
Plasma β-amyloid (Aβ )/Aβ levels have shown promise in identifying Aβ-PET positive individuals. This study explored the concordance and discordance of plasma Aβ /Aβ positivity (Plasma±) with CSF Aβ /Aβ positivity (CSF±) and Aβ-PET positivity (PET±) in older adults without dementia. Associations of A...
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Published in | Neurology Vol. 102; no. 7; p. e209205 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
09.04.2024
|
Online Access | Get more information |
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Summary: | Plasma β-amyloid
(Aβ
)/Aβ
levels have shown promise in identifying Aβ-PET positive individuals. This study explored the concordance and discordance of plasma Aβ
/Aβ
positivity (Plasma±) with CSF Aβ
/Aβ
positivity (CSF±) and Aβ-PET positivity (PET±) in older adults without dementia. Associations of Aβ deposition, cortical thickness, glucose metabolism, and microglial activation were also investigated.
We selected participants without dementia who had concurrent plasma Aβ
/Aβ
and Aβ-PET scans from the Alzheimer's Disease Neuroimaging Initiative cohort. Participants were categorized into Plasma±/PET± based on thresholds of composite
F-florbetapir (FBP) standardized uptake value ratio (SUVR) ≥1.11 and plasma Aβ
/Aβ
≤0.1218. Aβ-PET-negative individuals were further divided into Plasma±/CSF± (CSF Aβ
/Aβ
≤0.138), and the concordance and discordance of Aβ
/Aβ
in the plasma and CSF were investigated. Baseline and slopes of regional FBP SUVR were compared among Plasma±/PET± groups, and associations of regional FBP SUVR, FDG SUVR, cortical thickness, and CSF soluble Triggering Receptor Expressed on Myeloid Cell 2 (sTREM2) levels were analyzed.
One hundred eighty participants (mean age 72.7 years, 51.4% female, 96 cognitively unimpaired, and 84 with mild cognitive impairment) were included. We found that the proportion of Plasma+/PET- individuals was 6.14 times higher (odds ratio (OR) = 6.143, 95% confidence interval (CI) 2.740-16.185,
< 0.001) than that of Plasma-/PET+ individuals, and Plasma+/CSF- individuals showed 8.5 times larger percentage (OR = 8.5, 95% CI: 3.031-32.974,
< 0.001) than Plasma-/CSF+ individuals in Aβ-PET-negative individuals. Besides, Plasma+/PET- individuals exhibited faster (
< 0.05) Aβ accumulation predominantly in bilateral banks of superior temporal sulcus (BANKSSTS) and supramarginal, and superior parietal cortices compared with Plasma-/PET- individuals, despite no difference in baseline FBP SUVRs. In Plasma+/PET+ individuals, higher CSF sTREM2 levels correlated with slower BANKSSTS Aβ accumulation (standardized β (β
) = -0.418, 95% CI -0.681 to -0.154,
= 0.002). Conversely, thicker cortical thickness and higher glucose metabolism in supramarginal and superior parietal cortices were associated with faster (
< 0.05) CSF sTREM2 increase in Plasma+/PET- individuals rather than in Plasma+/PET+ individuals.
These findings suggest that plasma Aβ
/Aβ
abnormalities may predate CSF Aβ
/Aβ
and Aβ-PET abnormalities. Higher sTREM2-related microglial activation is linked to thicker cortical thickness and higher metabolism in early amyloidosis stages but tends to mitigate Aβ accumulation primarily at relatively advanced stages. |
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ISSN: | 1526-632X |
DOI: | 10.1212/WNL.0000000000209205 |