Entorhinal Cortex: Antemortem Cortical Thickness and Postmortem Neurofibrillary Tangles and Amyloid Pathology

Abstract

Background and purpose: The entorhinal cortex, a critical gateway between the neocortex and hippocampus, is one of the earliest regions affected by Alzheimer disease-associated neurofibrillary tangle pathology. Although our prior work has automatically delineated an MR imaging-based measure of the entorhinal cortex, whether antemortem entorhinal cortex thickness is associated with postmortem tangle burden within the entorhinal cortex is still unknown. Our objective was to evaluate the relationship between antemortem MRI measures of entorhinal cortex thickness and postmortem neuropathological measures.

Materials and methods: We evaluated 50 participants from the Rush Memory and Aging Project with antemortem structural T1-weighted MR imaging and postmortem neuropathologic assessments. Here, we focused on thickness within the entorhinal cortex as anatomically defined by our previously developed MR imaging parcellation system (Desikan-Killiany Atlas in FreeSurfer). Using linear regression, we evaluated the association between entorhinal cortex thickness and tangles and amyloid-β load within the entorhinal cortex and medial temporal and neocortical regions.

Results: We found a significant relationship between antemortem entorhinal cortex thickness and entorhinal cortex (P = .006) and medial temporal lobe tangles (P = .002); we found no relationship between entorhinal cortex thickness and entorhinal cortex (P = .09) and medial temporal lobe amyloid-β (P = .09). We also found a significant association between entorhinal cortex thickness and cortical tangles (P = .003) and amyloid-β (P = .01). We found no relationship between parahippocampal gyrus thickness and entorhinal cortex (P = .31) and medial temporal lobe tangles (P = .051).

Conclusions: Our findings indicate that entorhinal cortex-associated in vivo cortical thinning may represent a marker of postmortem medial temporal and neocortical Alzheimer disease pathology.

Fig 1.

Coronal T1-weighted MR imaging illustrating the anatomic location of the entorhinal cortex, which is medial to the rhinal sulcus (RS) and fusiform gyrus (FG) and inferior to the hippocampus (HIP), temporal horn of the lateral ventricle (THLV), and amygdala (AMYG) (upper left panel). 3D cortical (pial) representation is of the right cortical (pial) surface, delineating the location of the entorhinal cortex on the medial hemisphere of the cerebral cortex (lower right panel). STG indicates superior temporal gyrus; MTG, middle temporal gyrus; ITG, inferior temporal gyrus; TP, temporal pole; PHG, parahippocampal gyrus; LG, lingual gyrus; CUN, cuneus cortex; PCUN, precuneus; FG, fusiform gyrus; PCTL, paracentral lobule; SFG, superior frontal gyrus; MOFG, medial orbitofrontal gyrus; LOFG, lateral orbitofrontal gyrus; CC, corpus callosum; CING, cingulate cortex.

Fig 2.

Scatterplots illustrating the relationship between average entorhinal cortex thickness and average tangle density within the entorhinal cortex (upper left) and medial temporal lobe (MTL, upper right), and average amyloid-β load within the EC (lower left) and medial temporal lobe (lower right). Best-fit regression line, β-coefficients, and P values from the logistic regression model are included (for additional details see the text).

Fig 3.

Scatterplots illustrating the relationship between average entorhinal cortex thickness and composite tangle density (left) and amyloid-β load (right) within the cerebral cortex (see text for details). Best-fit regression line, β-coefficients, and P values from the logistic regression model are included (for additional details see the text).