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We investigated whether pre\u2010clinical changes in AD CSF biomarkers are reflected in blood DNA methylation (DNAm) levels in cognitively normal participants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      We profiled blood\u2010based DNAm with the EPIC array in participants without a diagnosis of cognitive impairment in the Emory Healthy Brain Study (EHBS;\n                      <jats:italic>N<\/jats:italic>\n                      \u00a0=\u00a0495), Alzheimer's Disease Neuroimaging Initiative (\n                      <jats:italic>N<\/jats:italic>\n                      \u00a0=\u00a0122), and Parkinson's Progression Markers Initiative (\n                      <jats:italic>N<\/jats:italic>\n                      \u00a0=\u00a0118) cohorts. Their CSF amyloid beta 42, total tau (t\u2010tau), and phosphorylated tau181 levels were quantified using Elecsys immunoassays. We conducted epigenome\u2010wide association studies to assess associations between DNAm and CSF biomarkers of AD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      In EHBS, no loci were Bonferroni significant after adjusting for confounding factors. In the meta\u2010analysis of all three cohorts, DNAm in cg22976567 (\n                      <jats:italic>LMNA<\/jats:italic>\n                      ) was significantly associated with higher CSF t\u2010tau levels.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Our study showed little evidence of an association between differential blood\u2010based DNAm and pre\u2010clinical AD CSF biomarkers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>\n                            We conducted one of the largest (\n                            <jats:italic>n<\/jats:italic>\n                            \u00a0=\u00a0735) blood DNA methylation (DNAm) studies of Alzheimer's disease cerebrospinal fluid (AD CSF) biomarkers.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>This is the first epigenome\u2010wide association study in cognitively normal participants examining AD CSF biomarkers.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Limited associations between blood DNAm and AD CSF biomarkers were identified.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  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