title: Few serum proteins mediate APOE's association with dementia.
abstract: The latent variable "δ" (for "dementia") appears to be uniquely responsible for the dementing aspects of cognitive impairment. Age, depression, gender and the apolipoprotein E (APOE) e4 allele are independently associated with δ. In this analysis, we explore serum proteins as potential mediators of APOE's specific association with δ in a large, ethnically diverse longitudinal cohort, the Texas Alzheimer's Research and Care Consortium (TARCC). APOE was associated only with C-Reactive Protein (CRP), Adiponectin (APN) and Amphiregulin (AREG), although the latter two's associations did not survive Bonferroni correction for multiple comparisons. All three proteins were associated with δ and had weak potential mediation effects on APOE's association with that construct. Our findings suggest that APOE's association with cognitive performance is specific to δ and partially mediated by serum inflammatory proteins. The majority of APOE's significant unadjusted effect on δ is unexplained. It may instead arise from direct central nervous system effects, possibly on native intelligence. If so, then APOE may exert a life-long influence over δ and therefore all-cause dementia risk.
authors.affiliation: Department of Psychiatry, the University of Texas Health Science Center, San Antonio, Texas, United States of America.|Department of Medicine, the University of Texas Health Science Center, San Antonio, Texas, United States of America.|Department of Family and Community Medicine, the University of Texas Health Science Center, San Antonio, Texas, United States of America.|South Texas Veterans' Health System Audie L. Murphy Division Geriatric Research Education and Clinical Care Center, San Antonio, Texas, United States of America.
authors.forename: Donald R
authors.initials: DR
authors.lastname: Royall
authors.affiliation: Department of Psychiatry, the University of Texas Health Science Center, San Antonio, Texas, United States of America.
authors.forename: Safa
authors.identifier: http://orcid.org/0000-0001-5030-3673
authors.initials: S
authors.lastname: Al-Rubaye
authors.affiliation: Department of Psychiatry, the Medical College of Georgia, Augusta, Georgia, United States of America.
authors.forename: Ram
authors.identifier: http://orcid.org/0000-0002-5202-5117
authors.initials: R
authors.lastname: Bishnoi
authors.affiliation: Department of Family and Community Medicine, the University of Texas Health Science Center, San Antonio, Texas, United States of America.
authors.forename: Raymond F
authors.initials: RF
authors.lastname: Palmer
mesh_terms: D000368:Aged; D001057:Apolipoproteins E / Q000502:physiology*; D001798:Blood Proteins / Q000502:physiology*; D003704:Dementia / Q000503:physiopathology*; D006801:Humans
chemical_list: D001057:Apolipoproteins E; D001798:Blood Proteins