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.

Entorhinal verrucae correlate with surface geometry

“…In our previous study, isosurface models were reconstructed from high resolution ex vivo MRI volumes scanned at high field (7.0T) and individual verruca were measured quantitatively for height, width, volume, and surface area on control cases (n=10 cases) [3]. Individual verrucae were systematically harvard.edu).…”

“…Retzius and later Klinger described these bumpy structures as the 'verrucae hippocampi' [1,2]. Since they are visible to the naked eye, several scientists have noted their presence [2][3][4][5][6], and in more recent work, the surface elevations have been referred to as the 'entorhinal verrucae' , which more accurately describes their location. The quantitative height of an individual verruca was demonstrated to be 0.13 mm for cognitive controls, with a range of 0.25 mm to 0.11 mm in height [3].…”

“…Since they are visible to the naked eye, several scientists have noted their presence [2][3][4][5][6], and in more recent work, the surface elevations have been referred to as the 'entorhinal verrucae' , which more accurately describes their location. The quantitative height of an individual verruca was demonstrated to be 0.13 mm for cognitive controls, with a range of 0.25 mm to 0.11 mm in height [3]. From our previous work, verrucae height correlated most strongly with qualitative observations, while verrucae volume was also significantly correlated, but verrucae width and surface area did little to differentiate the elevations from the underlying cortex.…”

“…Conversely, in Alzheimer's disease, the entorhinal verrucae disappear completely due to the massive cortical atrophy. Even in the earliest stages of Alzheimer's disease, a significant decrease in verrucae height, volume, surface area, and width has been demonstrated [3]. For these reasons, entorhinal verrucae make an appealing morphological structure to study in normal controls as well as the Alzheimer's disease population.…”

Memory Part 3: The Role of the Fornix and Clinical Cases

“…Pathologic processes that affect the hippocampal formation and parahippocampal gyrus, including the entorhinal cortex, correlate with specific types of memory deficits, [1][2][3][4][5][6][7][8][9][10] but the clinical consequences of lesions of the fornix have not been emphasized as often. A familiarity with the anatomy and imaging of the fornix helps to anticipate the clinical impact of pathology and treatment that involves this strategic structure.…”