title: Entorhinal verrucae geometry is coincident and correlates with Alzheimer's lesions: a combined neuropathology and high-resolution ex vivo MRI analysis.
abstract: Entorhinal cortex displays a distinctive organization in layer II and forms small elevations on its surface called entorhinal verrucae. In Alzheimer's disease, the verrucae disappear due to neurofibrillary tangle formation and neuronal death. Isosurface models were reconstructed from high-resolution ex vivo MRI volumes scanned at 7.0 T and individual verruca were measured quantitatively for height, width, volume, and surface area on control and mild Alzheimer's cases. Mean verruca height was 0.13 ± 0.04 mm for our cognitively normal (controls) sample set whereas for mild AD samples mean height was 0.11 mm ± 0.05 mm (p < 0.001) in entorhinal cortex (n = 10 cases). These quantitative methods were validated by a significant correlation of verrucae height and volume with qualitative verrucae ratings (n = 36 cases). Entorhinal surfaces were significantly different from other cortical heights such as, cingulate, frontal, occipital, parietal and temporal cortices. Colocalization of verrucae with entorhinal islands was confirmed in ex vivo MRI and, moreover, verrucae ratings were negatively correlated to Braak and Braak pathological stage. This study characterizes novel methods to measure individual entorhinal verruca size, and shows that verrucae size correlates to Alzheimer's pathology. Taken together, these results suggest that verrucae may have the potential to serve as an early and specific morphological marker for mild cognitive impairment and Alzheimer's disease.
authors.affiliation: Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Building 149-13th St., Room 2301, Charlestown, MA 02129, USA. jean@nmr.mgh.harvard.edu
authors.forename: Jean C
authors.initials: JC
authors.lastname: Augustinack
authors.forename: Kristen E
authors.initials: KE
authors.lastname: Huber
authors.forename: Gheorghe M
authors.initials: GM
authors.lastname: Postelnicu
authors.forename: Sita
authors.initials: S
authors.lastname: Kakunoori
authors.forename: Ruopeng
authors.initials: R
authors.lastname: Wang
authors.forename: André J W
authors.initials: AJ
authors.lastname: van der Kouwe
authors.forename: Lawrence L
authors.initials: LL
authors.lastname: Wald
authors.forename: Thor D
authors.initials: TD
authors.lastname: Stein
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Frosch
authors.forename: Bruce
authors.initials: B
authors.lastname: Fischl
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology*; D018728:Entorhinal Cortex / Q000473:pathology*; D005260:Female; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000473:pathology*; D013702:Temporal Lobe / Q000473:pathology