Affiliations: [a]
Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Nanjing, China
| [b]
Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China
Correspondence:
[*]
Correspondence to: Prof. Lan Tan, MD, PhD, Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University,Nanjing, 266071, China. Tel.: +86 21 52888160; Fax: +8621 62483421; E-mail: dr.tanlan@163.com.
Note: [1] Data used in preparation for this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (https://adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: https://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf.
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.
