CSF biomarkers of immune activation and Alzheimer’s disease for predicting cognitive impairment risk in the elderly

Francis Shue; Launia J. White; Rachel D. Hendrix; Jason Ulrich; Rachel L. Henson; William Knight; Yuka A. Martens; Ni Wang; Bhaskar Roy; Skylar C. Starling; Yingxue Ren; Chengjie Xiong; Yan W. Asmann; Jeremy A. Syrjanen; Maria Vassilaki; Michelle M. Mielke; Jigyasha Timsina; Yun Ju Sung; Carlos Cruchaga; David M. Holtzman; Guojun Bu; Ronald C. Petersen; Michael G. Heckman; Takahisa Kanekiyo

doi:10.1126/sciadv.adk3674

CSF biomarkers of immune activation and Alzheimer’s disease for predicting cognitive impairment risk in the elderly

Francis Shue, Launia J. White, Rachel D. Hendrix, Jason Ulrich, Rachel L. Henson, William Knight, Yuka A. Martens, Ni Wang, Bhaskar Roy, Skylar C. Starling, Yingxue Ren, Chengjie Xiong, Yan W. Asmann, Jeremy A. Syrjanen, Maria Vassilaki, Michelle M. Mielke, Jigyasha Timsina, Yun Ju Sung, Carlos Cruchaga, David M. HoltzmanGuojun Bu, Ronald C. Petersen, Michael G. Heckman, Takahisa Kanekiyo

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Abstract

The immune system substantially influences age-related cognitive decline and Alzheimer’s disease (AD) progression, affected by genetic and environmental factors. In a Mayo Clinic Study of Aging cohort, we examined how risk factors like APOE genotype, age, and sex affect inflammatory molecules and AD biomarkers in cerebrospinal fluid (CSF). Among cognitively unimpaired individuals over 65 (N = 298), we measured 365 CSF inflammatory molecules, finding age, sex, and diabetes status predominantly influencing their levels. We observed age-related correlations with AD biomarkers such as total tau, phosphorylated tau-181, neurofilament light chain (NfL), and YKL40. APOE4 was associated with lower Aβ42 and higher SNAP25 in CSF. We explored baseline variables predicting cognitive decline risk, finding age, CSF Aβ42, NfL, and REG4 to be independently correlated. Subjects with older age, lower Aβ42, higher NfL, and higher REG4 at baseline had increased cognitive impairment risk during follow-up. This suggests that assessing CSF inflammatory molecules and AD biomarkers could predict cognitive impairment risk in the elderly.

Original language	English (US)
Article number	eadk3674
Journal	Science Advances
Volume	10
Issue number	14
DOIs	https://doi.org/10.1126/sciadv.adk3674
State	Published - Apr 2024

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Shue, F., White, L. J., Hendrix, R. D., Ulrich, J., Henson, R. L., Knight, W., Martens, Y. A., Wang, N., Roy, B., Starling, S. C., Ren, Y., Xiong, C., Asmann, Y. W., Syrjanen, J. A., Vassilaki, M., Mielke, M. M., Timsina, J., Sung, Y. J., Cruchaga, C., ... Kanekiyo, T. (2024). CSF biomarkers of immune activation and Alzheimer’s disease for predicting cognitive impairment risk in the elderly. Science Advances, 10(14), Article eadk3674. https://doi.org/10.1126/sciadv.adk3674

Shue, F, White, LJ, Hendrix, RD, Ulrich, J, Henson, RL, Knight, W, Martens, YA, Wang, N, Roy, B, Starling, SC, Ren, Y, Xiong, C, Asmann, YW, Syrjanen, JA, Vassilaki, M, Mielke, MM, Timsina, J, Sung, YJ, Cruchaga, C, Holtzman, DM, Bu, G, Petersen, RC, Heckman, MG & Kanekiyo, T 2024, 'CSF biomarkers of immune activation and Alzheimer’s disease for predicting cognitive impairment risk in the elderly', Science Advances, vol. 10, no. 14, eadk3674. https://doi.org/10.1126/sciadv.adk3674

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title = "CSF biomarkers of immune activation and Alzheimer{\textquoteright}s disease for predicting cognitive impairment risk in the elderly",

abstract = "The immune system substantially influences age-related cognitive decline and Alzheimer{\textquoteright}s disease (AD) progression, affected by genetic and environmental factors. In a Mayo Clinic Study of Aging cohort, we examined how risk factors like APOE genotype, age, and sex affect inflammatory molecules and AD biomarkers in cerebrospinal fluid (CSF). Among cognitively unimpaired individuals over 65 (N = 298), we measured 365 CSF inflammatory molecules, finding age, sex, and diabetes status predominantly influencing their levels. We observed age-related correlations with AD biomarkers such as total tau, phosphorylated tau-181, neurofilament light chain (NfL), and YKL40. APOE4 was associated with lower Aβ42 and higher SNAP25 in CSF. We explored baseline variables predicting cognitive decline risk, finding age, CSF Aβ42, NfL, and REG4 to be independently correlated. Subjects with older age, lower Aβ42, higher NfL, and higher REG4 at baseline had increased cognitive impairment risk during follow-up. This suggests that assessing CSF inflammatory molecules and AD biomarkers could predict cognitive impairment risk in the elderly.",

author = "Francis Shue and White, {Launia J.} and Hendrix, {Rachel D.} and Jason Ulrich and Henson, {Rachel L.} and William Knight and Martens, {Yuka A.} and Ni Wang and Bhaskar Roy and Starling, {Skylar C.} and Yingxue Ren and Chengjie Xiong and Asmann, {Yan W.} and Syrjanen, {Jeremy A.} and Maria Vassilaki and Mielke, {Michelle M.} and Jigyasha Timsina and Sung, {Yun Ju} and Carlos Cruchaga and Holtzman, {David M.} and Guojun Bu and Petersen, {Ronald C.} and Heckman, {Michael G.} and Takahisa Kanekiyo",

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doi = "10.1126/sciadv.adk3674",

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AU - Ulrich, Jason

AU - Henson, Rachel L.

AU - Knight, William

AU - Martens, Yuka A.

AU - Wang, Ni

AU - Roy, Bhaskar

AU - Starling, Skylar C.

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AU - Xiong, Chengjie

AU - Asmann, Yan W.

AU - Syrjanen, Jeremy A.

AU - Vassilaki, Maria

AU - Mielke, Michelle M.

AU - Timsina, Jigyasha

AU - Sung, Yun Ju

AU - Cruchaga, Carlos

AU - Holtzman, David M.

AU - Bu, Guojun

AU - Petersen, Ronald C.

AU - Heckman, Michael G.

AU - Kanekiyo, Takahisa

PY - 2024/4

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N2 - The immune system substantially influences age-related cognitive decline and Alzheimer’s disease (AD) progression, affected by genetic and environmental factors. In a Mayo Clinic Study of Aging cohort, we examined how risk factors like APOE genotype, age, and sex affect inflammatory molecules and AD biomarkers in cerebrospinal fluid (CSF). Among cognitively unimpaired individuals over 65 (N = 298), we measured 365 CSF inflammatory molecules, finding age, sex, and diabetes status predominantly influencing their levels. We observed age-related correlations with AD biomarkers such as total tau, phosphorylated tau-181, neurofilament light chain (NfL), and YKL40. APOE4 was associated with lower Aβ42 and higher SNAP25 in CSF. We explored baseline variables predicting cognitive decline risk, finding age, CSF Aβ42, NfL, and REG4 to be independently correlated. Subjects with older age, lower Aβ42, higher NfL, and higher REG4 at baseline had increased cognitive impairment risk during follow-up. This suggests that assessing CSF inflammatory molecules and AD biomarkers could predict cognitive impairment risk in the elderly.

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CSF biomarkers of immune activation and Alzheimer’s disease for predicting cognitive impairment risk in the elderly

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