Danni Li, William G Mantyh, Lu Men, Ishika Jain, Matthew Glittenberg, Binchong An, Lin Zhang, Ling Li
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We used analysis of covariance testing adjusting for covariates, followed by Tukey post hoc pairwise comparisons, to compare CSF soluble triggering receptor expressed on myeloid cells-2 (sTREM2) across four participant groups: CSF+ <sub>Aβ42</sub> with CSF- <sub>p-tau/Aβ42</sub>, CSF- <sub>Aβ42</sub> with CSF+ <sub>p-tau/Aβ42</sub>, and concordant CSF<sub>Aβ42</sub>/CSF<sub>p-tau/Aβ42</sub>. We also compared sTREM2 across discordant and concordant CSF<sub>Aβ42</sub>/PET.</p><p><strong>Results: </strong>Regardless of Aβ PET status, CSF+<sub>Aβ42</sub> with CSF-<sub>p-tau/Aβ42</sub> had lower sTREM2 than CSF-<sub>Aβ42</sub> with CSF+<sub>p-tau/Aβ42</sub>. CSF sTREM2 was similarly also associated with discordant CSF Aβ42 /PET.</p><p><strong>Discussion: </strong>Our study suggests the potential roles of sTREM2 in discordant CSF Aβ<sub>42</sub> and p-tau181/Aβ<sub>42</sub> and discordant CSF<sub>Aβ42</sub>/PET. Low- and high-CSF sTREM2 may affect the accuracy of p-tau181/Aβ<sub>42</sub> during the clinical work-up of AD.</p><p><strong>Highlights: </strong>17% of non-demented older adults had discordant CSF Aβ<sub>42</sub> versus p-tau181/Aβ<sub>42</sub>.sTREM2 differed between discordant cases of CSF Aβ<sub>42</sub> versus p-tau181/Aβ<sub>42</sub>.20% of non-demented older adults had discordant CSF Aβ<sub>42</sub> versus Aβ PET.sTREM2 also differed between discordant cases of CSF Aβ<sub>42</sub> versus Aβ PET.p-tau181/Aβ<sub>42</sub> may miss 6.7% of PET+ non-demented older adults with low sTREM2.</p>","PeriodicalId":53226,"journal":{"name":"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring","volume":"17 1","pages":"e70072"},"PeriodicalIF":4.0000,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11736621/pdf/","citationCount":"0","resultStr":"{\"title\":\"sTREM2 in discordant CSF Aβ<sub>42</sub> and p-tau181.\",\"authors\":\"Danni Li, William G Mantyh, Lu Men, Ishika Jain, Matthew Glittenberg, Binchong An, Lin Zhang, Ling Li\",\"doi\":\"10.1002/dad2.70072\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Little is known about the factors underpinning discordant cerebrospinal fluid (CSF) amyloid beta (Aβ)<sub>42</sub> versus p-tau181/Aβ<sub>42</sub> or CSF Aβ<sub>42</sub> versus Aβ positron emission tomography (PET).</p><p><strong>Methods: </strong>We stratified 570 non-demented Alzheimer's Disease Neuroimaging Initiative (ADNI) participants by Aβ PET and further by CSF Aβ<sub>42</sub> or p-tau181/Aβ<sub>42</sub>. We used analysis of covariance testing adjusting for covariates, followed by Tukey post hoc pairwise comparisons, to compare CSF soluble triggering receptor expressed on myeloid cells-2 (sTREM2) across four participant groups: CSF+ <sub>Aβ42</sub> with CSF- <sub>p-tau/Aβ42</sub>, CSF- <sub>Aβ42</sub> with CSF+ <sub>p-tau/Aβ42</sub>, and concordant CSF<sub>Aβ42</sub>/CSF<sub>p-tau/Aβ42</sub>. We also compared sTREM2 across discordant and concordant CSF<sub>Aβ42</sub>/PET.</p><p><strong>Results: </strong>Regardless of Aβ PET status, CSF+<sub>Aβ42</sub> with CSF-<sub>p-tau/Aβ42</sub> had lower sTREM2 than CSF-<sub>Aβ42</sub> with CSF+<sub>p-tau/Aβ42</sub>. CSF sTREM2 was similarly also associated with discordant CSF Aβ42 /PET.</p><p><strong>Discussion: </strong>Our study suggests the potential roles of sTREM2 in discordant CSF Aβ<sub>42</sub> and p-tau181/Aβ<sub>42</sub> and discordant CSF<sub>Aβ42</sub>/PET. 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引用次数: 0
摘要
关于脑脊液（CSF）淀粉样蛋白β (Aβ)42与p-tau181/Aβ42或CSF Aβ42与Aβ正电子发射断层扫描（PET）不一致的因素知之甚少。方法：我们通过Aβ PET和CSF Aβ42或p-tau181/Aβ42对570名非痴呆性阿尔茨海默病神经影像学计划（ADNI）参与者进行分层。我们使用协方差检验分析校正协变量，随后进行Tukey事后两两比较，比较了四个参与者组CSF+ Aβ42与CSF- p-tau/ a - β42、CSF- Aβ42与CSF+ p-tau/ a - β42和一致性CSF fa β42/CSFp-tau/ a - β42在髓样细胞-2上表达的CSF可溶性触发受体（sTREM2）。我们还比较了不一致和一致CSFAβ42/PET的sTREM2。结果：无论Aβ PET状态如何，CSF+Aβ42 + CSF-p-tau/Aβ42的strem - 2均低于CSF+p-tau/Aβ42的CSF-Aβ42。脑脊液sTREM2同样也与脑脊液Aβ42 /PET不一致相关。讨论：我们的研究提示sTREM2在脑脊液Aβ42和p-tau181/Aβ42不一致以及脑脊液Aβ42/PET不一致中的潜在作用。在阿尔茨海默病的临床检查中，低和高csf sTREM2可能会影响p-tau181/ a - β42的准确性。重点：17%的非痴呆老年人脑脊液Aβ42与p-tau181/Aβ42不一致。脑脊液Aβ42与p-tau181/Aβ不一致病例的sTREM2差异有42.20%的非痴呆老年人脑脊液Aβ42与Aβ PET不一致。脑脊液Aβ42与Aβ PET不一致病例的sTREM2也存在差异。p-tau181/ a - β42可能错过6.7%的PET+低sTREM2非痴呆老年人。
Introduction: Little is known about the factors underpinning discordant cerebrospinal fluid (CSF) amyloid beta (Aβ)42 versus p-tau181/Aβ42 or CSF Aβ42 versus Aβ positron emission tomography (PET).
Methods: We stratified 570 non-demented Alzheimer's Disease Neuroimaging Initiative (ADNI) participants by Aβ PET and further by CSF Aβ42 or p-tau181/Aβ42. We used analysis of covariance testing adjusting for covariates, followed by Tukey post hoc pairwise comparisons, to compare CSF soluble triggering receptor expressed on myeloid cells-2 (sTREM2) across four participant groups: CSF+ Aβ42 with CSF- p-tau/Aβ42, CSF- Aβ42 with CSF+ p-tau/Aβ42, and concordant CSFAβ42/CSFp-tau/Aβ42. We also compared sTREM2 across discordant and concordant CSFAβ42/PET.
Results: Regardless of Aβ PET status, CSF+Aβ42 with CSF-p-tau/Aβ42 had lower sTREM2 than CSF-Aβ42 with CSF+p-tau/Aβ42. CSF sTREM2 was similarly also associated with discordant CSF Aβ42 /PET.
Discussion: Our study suggests the potential roles of sTREM2 in discordant CSF Aβ42 and p-tau181/Aβ42 and discordant CSFAβ42/PET. Low- and high-CSF sTREM2 may affect the accuracy of p-tau181/Aβ42 during the clinical work-up of AD.
Highlights: 17% of non-demented older adults had discordant CSF Aβ42 versus p-tau181/Aβ42.sTREM2 differed between discordant cases of CSF Aβ42 versus p-tau181/Aβ42.20% of non-demented older adults had discordant CSF Aβ42 versus Aβ PET.sTREM2 also differed between discordant cases of CSF Aβ42 versus Aβ PET.p-tau181/Aβ42 may miss 6.7% of PET+ non-demented older adults with low sTREM2.
期刊介绍：
Alzheimer''s & Dementia: Diagnosis, Assessment & Disease Monitoring (DADM) is an open access, peer-reviewed, journal from the Alzheimer''s Association® that will publish new research that reports the discovery, development and validation of instruments, technologies, algorithms, and innovative processes. Papers will cover a range of topics interested in the early and accurate detection of individuals with memory complaints and/or among asymptomatic individuals at elevated risk for various forms of memory disorders. The expectation for published papers will be to translate fundamental knowledge about the neurobiology of the disease into practical reports that describe both the conceptual and methodological aspects of the submitted scientific inquiry. Published topics will explore the development of biomarkers, surrogate markers, and conceptual/methodological challenges. Publication priority will be given to papers that 1) describe putative surrogate markers that accurately track disease progression, 2) biomarkers that fulfill international regulatory requirements, 3) reports from large, well-characterized population-based cohorts that comprise the heterogeneity and diversity of asymptomatic individuals and 4) algorithmic development that considers multi-marker arrays (e.g., integrated-omics, genetics, biofluids, imaging, etc.) and advanced computational analytics and technologies.
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