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Entorhinal verrucae geometry is coincident and correlates with Alzheimer’s lesions: a combined neuropathology and high-resolution ex vivo MRI analysis

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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.

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Acknowledgments

We would like to thank those who donated tissue; their generous donation made this work possible. We also thank David Salat for comments and discussion. Support for this research was provided in part by the National Center for Research Resources (P41-RR14075, and the NCRR BIRN Morphometric Project BIRN002, U24 RR021382), the National Institute for Biomedical Imaging and Bioengineering (R01EB006758), the National Institute on Aging (AG022381) and (AG028521), the National Center for Alternative Medicine (RC1AT005728-01), the National Institute for Neurological Disorders and Stroke (R01 NS052585-01, 1R21NS072652-01, 1R01NS070963), and was made possible by the resources provided by Shared Instrumentation Grants 1S10RR023401, 1S10RR019307, and 1S10RR023043. Additional support was provided by The Autism and Dyslexia Project funded by the Ellison Medical Foundation and by the NIH Blueprint for Neuro-science Research (U01-MH093765, part of the multi-institutional Human Connectome Project).

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Authors and Affiliations

  1. Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Building 149–13th St., Room 2301, Charlestown, MA, 02129, USA

    Jean C. Augustinack, Kristen E. Huber, Sita Kakunoori, Ruopeng Wang, André J. W. van der Kouwe, Lawrence L. Wald & Bruce Fischl

  2. Google, Inc., 110 Brandschenkestrasse, 8002, Zurich, Switzerland

    Gheorghe M. Postelnicu

  3. Department of Neuropathology, Massachusetts General Hospital, 55 Fruit St., Boston, MA, 02115, USA

    Thor D. Stein & Matthew P. Frosch

  4. CSAIL, MIT, 32 Vassar Street, Cambridge, MA, 02139, USA

    Bruce Fischl

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  1. Jean C. Augustinack
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Correspondence to Jean C. Augustinack.

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Augustinack, J.C., Huber, K.E., Postelnicu, G.M. et al. Entorhinal verrucae geometry is coincident and correlates with Alzheimer’s lesions: a combined neuropathology and high-resolution ex vivo MRI analysis. Acta Neuropathol 123, 85–96 (2012). https://doi.org/10.1007/s00401-011-0929-5

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