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 |
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09.04.2024
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Abstract | 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. |
---|---|
AbstractList | 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. |
Author | Guo, Tengfei Shi, Dai Cai, Yue Lan, Guoyu Zhou, Liemin Jiang, Yanni Chen, Linting |
AuthorAffiliation | From the Institute of Biomedical Engineering (Y.C., G.L., L.C., T.G.), Shenzhen Bay Laboratory; Neurology Medicine Center (D.S., L.Z.), The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China; Department of Psychology (Y.J.), University of Texas at Austin; and Institute of Biomedical Engineering (T.G.), Peking University Shenzhen Graduate School, China |
AuthorAffiliation_xml | – name: From the Institute of Biomedical Engineering (Y.C., G.L., L.C., T.G.), Shenzhen Bay Laboratory; Neurology Medicine Center (D.S., L.Z.), The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China; Department of Psychology (Y.J.), University of Texas at Austin; and Institute of Biomedical Engineering (T.G.), Peking University Shenzhen Graduate School, China |
Author_xml | – sequence: 1 givenname: Yue surname: Cai fullname: Cai, Yue organization: From the Institute of Biomedical Engineering (Y.C., G.L., L.C., T.G.), Shenzhen Bay Laboratory; Neurology Medicine Center (D.S., L.Z.), The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China; Department of Psychology (Y.J.), University of Texas at Austin; and Institute of Biomedical Engineering (T.G.), Peking University Shenzhen Graduate School, China – sequence: 2 givenname: Dai surname: Shi fullname: Shi, Dai organization: From the Institute of Biomedical Engineering (Y.C., G.L., L.C., T.G.), Shenzhen Bay Laboratory; Neurology Medicine Center (D.S., L.Z.), The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China; Department of Psychology (Y.J.), University of Texas at Austin; and Institute of Biomedical Engineering (T.G.), Peking University Shenzhen Graduate School, China – sequence: 3 givenname: Guoyu surname: Lan fullname: Lan, Guoyu organization: From the Institute of Biomedical Engineering (Y.C., G.L., L.C., T.G.), Shenzhen Bay Laboratory; Neurology Medicine Center (D.S., L.Z.), The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China; Department of Psychology (Y.J.), University of Texas at Austin; and Institute of Biomedical Engineering (T.G.), Peking University Shenzhen Graduate School, China – sequence: 4 givenname: Linting surname: Chen fullname: Chen, Linting organization: From the Institute of Biomedical Engineering (Y.C., G.L., L.C., T.G.), Shenzhen Bay Laboratory; Neurology Medicine Center (D.S., L.Z.), The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China; Department of Psychology (Y.J.), University of Texas at Austin; and Institute of Biomedical Engineering (T.G.), Peking University Shenzhen Graduate School, China – sequence: 5 givenname: Yanni surname: Jiang fullname: Jiang, Yanni organization: From the Institute of Biomedical Engineering (Y.C., G.L., L.C., T.G.), Shenzhen Bay Laboratory; Neurology Medicine Center (D.S., L.Z.), The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China; Department of Psychology (Y.J.), University of Texas at Austin; and Institute of Biomedical Engineering (T.G.), Peking University Shenzhen Graduate School, China – sequence: 6 givenname: Liemin surname: Zhou fullname: Zhou, Liemin organization: From the Institute of Biomedical Engineering (Y.C., G.L., L.C., T.G.), Shenzhen Bay Laboratory; Neurology Medicine Center (D.S., L.Z.), The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China; Department of Psychology (Y.J.), University of Texas at Austin; and Institute of Biomedical Engineering (T.G.), Peking University Shenzhen Graduate School, China – sequence: 7 givenname: Tengfei orcidid: 0000-0003-2982-0865 surname: Guo fullname: Guo, Tengfei organization: From the Institute of Biomedical Engineering (Y.C., G.L., L.C., T.G.), Shenzhen Bay Laboratory; Neurology Medicine Center (D.S., L.Z.), The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China; Department of Psychology (Y.J.), University of Texas at Austin; and Institute of Biomedical Engineering (T.G.), Peking University Shenzhen Graduate School, China |
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Snippet | Plasma β-amyloid
(Aβ
)/Aβ
levels have shown promise in identifying Aβ-PET positive individuals. This study explored the concordance and discordance of plasma... |
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SubjectTerms | Aged Alzheimer Disease - metabolism Amyloid beta-Peptides - metabolism Amyloidosis Biomarkers Cognitive Dysfunction - metabolism Female Glucose Humans Male Microglia - metabolism Peptide Fragments Positron-Emission Tomography - methods tau Proteins |
Title | Association of β-Amyloid, Microglial Activation, Cortical Thickness, and Metabolism in Older Adults Without Dementia |
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