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Home > Soluble TREM2, Alzheimer's Disease Pathology, and Risk for Progression of Cerebral Small Vessel Disease: A Longitudinal Study.

TitleSoluble TREM2, Alzheimer's Disease Pathology, and Risk for Progression of Cerebral Small Vessel Disease: A Longitudinal Study.
Publication TypeJournal Article
Year of Publication2023
AuthorsWu, C, Ma, Y-H, Hu, H, Zhao, B, Tan, L
Corporate AuthorsAlzheimer’s Disease Neuroimaging Initiative
JournalJ Alzheimers Dis
Volume92
Issue1
Pagination311-322
Date Published2023
ISSN1875-8908
KeywordsAlzheimer Disease, Biomarkers, Cerebral Small Vessel Diseases, Humans, Longitudinal Studies, Membrane Glycoproteins, Myeloid Cells, Neuroinflammatory Diseases, Receptors, Immunologic
Abstract

BackgroundUntil recently, studies on associations between neuroinflammation in vivo and cerebral small vessel disease (CSVD) are scarce. Cerebrospinal fluid (CSF) levels of soluble triggering receptor expressed on myeloid cells 2 (sTREM2), a candidate biomarker of microglial activation and neuroinflammation, were found elevated in Alzheimer's disease (AD), but they have not been fully explored in CSVD.ObjectiveTo determine whether CSF sTREM2 levels are associated with the increased risk of CSVD progression.MethodsA total of 426 individuals from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database were included in this study. All participants underwent measurements of CSF sTREM2 and AD pathology (Aβ1-42, P-tau181P). The progression of CSVD burden and imaging markers, including cerebral microbleeds (CMBs), white matter hyperintensities and lacunes, were estimated based on neuroimaging changes. Logistic regression and moderation effect models were applied to explore associations of sTREM2 with CSVD progression and AD pathology.Results Higher CSF sTREM2 levels at baseline were associated with increased CSVD burden (OR = 1.28 [95% CI, 1.01-1.62]) and CMBs counts (OR = 1.32 [95% CI, 1.03-1.68]). Similarly, increased change rates of CSF sTREM2 might predict elevated CMBs counts (OR = 1.44 [95% CI, 1.05-1.98]). Participants with AD pathology (Aβ1-42 and P-tau181P) showed a stronger association between CSF sTREM2 and CSVD progression.ConclusionThis longitudinal study found a positive association between CSF sTREM2 and CSVD progression, suggesting that neuroinflammation might promote CSVD. Furthermore, neuroinflammation could be a shared pathogenesis of CSVD and AD at the early stage. Targeting neuroinflammation to intervene the progression of CSVD and AD warrants further investigation.

DOI10.3233/JAD-220731
Alternate JournalJ Alzheimers Dis
PubMed ID36744335
Grant ListU01 AG024904 / AG / NIA NIH HHS / United States
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Source URL: https://www.j-alz.com/content/soluble-trem2-alzheimers-disease-pathology-and-risk-progression-cerebral-small-vessel