Shared vulnerability of two synaptically-connected medial temporal lobe areas to age and cognitive decline: A seven tesla magnetic resonance imaging study

Geoffrey A. Kerchner, Jeffrey D. Bernstein, Michelle C. Fenesy, Gayle K. Deutsch, Manojkumar Saranathan, Michael M. Zeineh, Brian K. Rutt

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

The medial temporal lobe (MTL) is the first brain area to succumb to neurofibrillary tau pathology in Alzheimer's disease (AD). Postmortem human tissue evaluation suggests that this pathology propagates in an ordered manner, with the entorhinal cortex (ERC) and then CA1 stratum radiatum and stratum lacunosum-moleculare (CA1-SRLM)-two monosynaptically connected structures-exhibiting selective damage. Here, we hypothesized that, if ERC and CA1-SRLM share an early vulnerability to AD pathology, then atrophy should occur in a proportional manner between the two structures. We tested this hypothesis in living humans, using ultra-high field 7.0 T MRI to make fine measurements of MTL microstructure. Among a pool of age-matched healthy controls and patients with amnestic mild cognitive impairment and mild AD, we found a significant correlation between ERC and CA1-SRLM size that could not be explained by global atrophy affecting the MTL. Of the various structures that contribute axons or dendrites into the CA1-SRLM neuropil, only ERC emerged as a significant predictor of CA1-SRLM size in a linear regression analysis. In contrast, other synaptically connected elements of the MTL did not exhibit size correlations. CA1-SRLM and ERC structural covariance was significant for older controls and not patients, whereas the opposite pattern emerged for a correlation between CA1-SRLM and episodic memory performance. Interestingly, CA1-SRLM and ERC were the only MTL structures to atrophy in older controls relative to a younger comparison group. Together, these findings suggest that ERC and CA1-SRLM share vulnerability to both age and AD-associated atrophy.

Original languageEnglish (US)
Pages (from-to)16666-16672
Number of pages7
JournalJournal of Neuroscience
Volume33
Issue number42
DOIs
StatePublished - 2013
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)

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