Early amygdala and ERC atrophy linked to 3D reconstruction of rostral neurofibrillary tau tangle pathology in Alzheimer’s disease

Kaitlin M. Stouffer; Claire Chen; Sue Kulason; Eileen Xu; Menno P. Witter; Can Ceritoglu; Marilyn S. Albert; Susumu Mori; Juan Troncoso; Daniel J. Tward; Michael I. Miller

NeuroImage: Clinical (Jan 2023)

Early amygdala and ERC atrophy linked to 3D reconstruction of rostral neurofibrillary tau tangle pathology in Alzheimer’s disease

Kaitlin M. Stouffer,
Claire Chen,
Sue Kulason,
Eileen Xu,
Menno P. Witter,
Can Ceritoglu,
Marilyn S. Albert,
Susumu Mori,
Juan Troncoso,
Daniel J. Tward,
Michael I. Miller

Affiliations

Kaitlin M. Stouffer: Department of Biomedical Engineering, Johns Hopkins University, 3400 N Charles St, Baltimore 21218, MD, USA; Corresponding author.
Claire Chen: Department of Biomedical Engineering, Johns Hopkins University, 3400 N Charles St, Baltimore 21218, MD, USA
Sue Kulason: Department of Biomedical Engineering, Johns Hopkins University, 3400 N Charles St, Baltimore 21218, MD, USA
Eileen Xu: Department of Biomedical Engineering, Johns Hopkins University, 3400 N Charles St, Baltimore 21218, MD, USA
Menno P. Witter: Kavli Institute for Systems Neuroscience, Norwegian University of Science and Technology, 7491 Trondheim, Norway
Can Ceritoglu: Department of Biomedical Engineering, Johns Hopkins University, 3400 N Charles St, Baltimore 21218, MD, USA
Marilyn S. Albert: Departments of Neurology, Johns Hopkins School of Medicine, 733 N Broadway, Baltimore 21205, MD, USA
Susumu Mori: Department of Radiology, Johns Hopkins School of Medicine, 733 N Broadway, Baltimore 21205, MD, USA
Juan Troncoso: Department of Pathology, Johns Hopkins School of Medicine, 733 N Broadway, Baltimore 21205, MD, USA
Daniel J. Tward: Departments of Computational Medicine and Neurology, University of California, Los Angeles, UCLA Brain Mapping Center, 660 Charles E. Young Drive South, Los Angeles 90095, CA, USA
Michael I. Miller: Department of Biomedical Engineering, Johns Hopkins University, 3400 N Charles St, Baltimore 21218, MD, USA

Journal volume & issue: Vol. 38
p. 103374

Abstract

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Previous research has emphasized the unique impact of Alzheimer’s Disease (AD) pathology on the medial temporal lobe (MTL), a reflection that tau pathology is particularly striking in the entorhinal and transentorhinal cortex (ERC, TEC) early in the course of disease. However, other brain regions are affected by AD pathology during its early phases. Here, we use longitudinal diffeomorphometry to measure the atrophy rate from MRI of the amygdala compared with that in the ERC and TEC in cognitively unimpaired (CU) controls, CU individuals who progressed to mild cognitive impairment (MCI), and individuals with MCI who progressed to dementia of the AD type (DAT), using a dataset from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Our results show significantly higher atrophy rates of the amygdala in both groups of ‘converters’ (CU→MCI, MCI→DAT) compared to controls, with rates of volume loss comparable to rates of thickness loss in the ERC and TEC. We localize atrophy within the amygdala within each of these groups using fixed effects modeling. Controlling for the familywise error rate highlights the medial regions of the amygdala as those with significantly higher atrophy in both groups of converters than in controls. Using our recently developed method, referred to as Projective LDDMM, we map measures of neurofibrillary tau tangles (NFTs) from digital pathology to MRI atlases and reconstruct dense 3D spatial distributions of NFT density within regions of the MTL. The distribution of NFTs is consistent with the spatial distribution of MR measured atrophy rates, revealing high densities (and atrophy) in the amygdala (particularly medial), ERC, and rostral third of the MTL. The similarity of the location of NFTs in AD and shape changes in a well-defined clinical population suggests that amygdalar atrophy rate, as measured through MRI may be a viable biomarker for AD.

Published in NeuroImage: Clinical

ISSN: 2213-1582 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General): Computer applications to medicine. Medical informatics; Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry: Neurology. Diseases of the nervous system
Website: http://www.journals.elsevier.com/neuroimage-clinical/

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