Anterior Cingulate Structure and Perfusion is Associated with Cerebrospinal Fluid Tau among Cognitively Normal Older Adult APOE ε4 Carriers

Evidence suggests the epsilon 4 allele of the apolipoprotein E (APOE) gene may accelerate an age-related process of cortical thickening and cerebral blood flow (CBF) reduction in the anterior cingulate cortex (ACC). Although the neural basis of this association remains unclear, evidence suggests it might reflect early neurodegenerative processes. However, to date, associations between cerebrospinal fluid (CSF) biomarkers of neurodegeneration, such as CSF tau, and APOE-related alterations in ACC cortical thickness (CTH) and CBF have yet to be explored. The current study explored the interaction of CSF tau and APOE genotype (epsilon 4+, epsilon 4-) on FreeSurfer-derived CTH and arterial spin labeling MRI-measured resting CBF in the ACC (caudal ACC [cACC] and rostral ACC [rACC]) among a sample of 45 cognitively normal older adults. Secondary analyses also examined associations between APOE, CTH/CBF, and cognitive performance. In the cACC, higher CSF tau was associated with higher CTH and lower CBF in epsilon 4+, whereas these relationships were not evident in epsilon 4-. In the rACC, higher CSF tau was associated with higher CTH for both epsilon 4+ and epsilon 4-, and with lower CBF only in epsilon 4+. Significant interactions of CSF tau and APOE on CTH/CBF were not observed in two posterior reference regions implicated in Alzheimer's disease. Secondary analyses revealed a negative relationship between cACC CTH and executive functioning in epsilon 4+ and a positive relationship in epsilon 4-. Findings suggest the presence of an epsilon 4-related pattern of increased CTH and reduced CBF in the ACC that is associated with biomarkers of neurodegeneration and subtle decrements in cognition.