title: Neuromarkers of the common angiotensinogen polymorphism in healthy older adults: A comprehensive assessment of white matter integrity and cognition.
abstract: The common angiotensinogen (AGT) M268T polymorphism (rs699; historically referred to as M235T) has been identified as a significant risk factor for cerebrovascular pathologies, yet it is unclear if healthy older adults carrying the threonine amino acid variant have a greater risk for white matter damage in specific fiber tracts. Further, the impact of the threonine variant on cognitive function remains unknown. The present study utilized multiple indices of diffusion tensor imaging (DTI) and neuropsychological assessment to examine the integrity of specific white matter tracts and cognition between individuals with homozygous genotypes of M268T (MetMet n=27, ThrThr n=27). Differences in subcortical hyperintensity (SH) volume were also examined between groups. Results indicated that the threonine variant was associated with significantly reduced integrity in the superior longitudinal fasciculus (SLF) and the cingulate gyrus segment of the cingulum bundle (cingulum CG) compared to those with the methionine variant, and poorer cognitive performance on tests of attention/processing speed and language. Despite these associations, integrity of these tracts did not significantly mediate relationships between cognition and genetic status, and SH did not differ significantly between groups. Collectively our results suggest that the threonine variant of M268T is a significant risk factor for abnormalities in specific white matter tracts and cognitive domains in healthy older adults, independent of SH burden.
authors: University of Missouri-St. Louis, Department of Psychological Sciences, 1 University Blvd., Stadler Hall 442A, St. Louis, MO 63121, USA. Electronic address: LSalminen@mail.umsl.edu.
authors: Lauren E
authors: LE
authors: Salminen
authors: Neuroscience Research Australia, Barker Street Randwick, Sydney, NSW 2031, Australia; School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia.
authors: Peter R
authors: PR
authors: Schofield
authors: Neuroscience Research Australia, Barker Street Randwick, Sydney, NSW 2031, Australia.
authors: Kerrie D
authors: KD
authors: Pierce
authors: Brown University, Department of Biostatistics and Center for Statistical Sciences, Providence, RI 02912, USA.
authors: Yi
authors: Y
authors: Zhao
authors: Brown University, Department of Biostatistics and Center for Statistical Sciences, Providence, RI 02912, USA.
authors: Xi
authors: X
authors: Luo
authors: Brown University, Department of Biostatistics and Center for Statistical Sciences, Providence, RI 02912, USA.
authors: Youdan
authors: Y
authors: Wang
authors: Brown University, Computer Science Department, Providence, RI 02912, USA.
authors: David H
authors: DH
authors: Laidlaw
authors: Brown University, Computer Science Department, Providence, RI 02912, USA.
authors: Ryan P
authors: RP
authors: Cabeen
authors: Washington University School of Medicine, Mallinckrodt Institute of Radiology, 510 S. Kingshighway, St. Louis, MO 63110, USA.
authors: Thomas E
authors: TE
authors: Conturo
authors: Missouri Institute of Mental Health,4633 World Parkway Circle, Berkeley, MO 63134-3115, USA.
authors: David F
authors: DF
authors: Tate
authors: Washington University School of Medicine, Mallinckrodt Institute of Radiology, 510 S. Kingshighway, St. Louis, MO 63110, USA.
authors: Erbil
authors: E
authors: Akbudak
authors: Vanderbilt University Medical Center, 1211 Medical Center Drive, Nashville, TN 37232, USA.
authors: Elizabeth M
authors: EM
authors: Lane
authors: Missouri Institute of Mental Health,4633 World Parkway Circle, Berkeley, MO 63134-3115, USA.
authors: Jodi M
authors: JM
authors: Heaps
authors: University of Missouri-St. Louis, Department of Psychological Sciences, 1 University Blvd., Stadler Hall 442A, St. Louis, MO 63121, USA.
authors: Jacob D
authors: JD
authors: Bolzenius
authors: University of Missouri-St. Louis, Department of Psychological Sciences, 1 University Blvd., Stadler Hall 442A, St. Louis, MO 63121, USA.
authors: Laurie M
authors: LM
authors: Baker
authors: University of Missouri-St. Louis, Department of Psychological Sciences, 1 University Blvd., Stadler Hall 442A, St. Louis, MO 63121, USA.
authors: Lee M
authors: LM
authors: Cagle
authors: University of Missouri-St. Louis, Department of Psychological Sciences, 1 University Blvd., Stadler Hall 442A, St. Louis, MO 63121, USA; Missouri Institute of Mental Health,4633 World Parkway Circle, Berkeley, MO 63134-3115, USA.
authors: Robert H
authors: RH
authors: Paul
mesh_terms: D000368:Aged; D000808:Angiotensinogen / Q000235:genetics*; D001288:Attention / Q000502:physiology*; D015415:Biomarkers; D003071:Cognition / Q000502:physiology*; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D007802:Language; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000033:anatomy & histology / Q000473:pathology; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide; D011597:Psychomotor Performance / Q000502:physiology*; D012307:Risk Factors; D013912:Threonine; D066127:White Matter / Q000033:anatomy & histology* / Q000473:pathology
chemical_list: C534931:AGT protein, human; D015415:Biomarkers; D000808:Angiotensinogen; D013912:Threonine
keywords: AGT; Cognition; M235T; M268T; White matter; rs699