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Rostral associations of MRI atrophy of the amygdala and entorhinal cortex across the AD spectrum

Michael I Miller1,2,3,4,5, Yi Xie2,3, Kaitlin M Stouffer1

  • 1Department of Biomedical Engineering, Johns Hopkins University, 3400 N Charles St, Baltimore, 21218, MD, USA.

Neuroimage. Reports
|August 20, 2026
PubMed

Insights

Brain imaging reveals early changes in the amygdala, entorhinal cortex (ERC), and transentorhinal cortex (TEC) in Alzheimer's disease. Atrophy in these regions correlates with tau pathology, indicating their role in disease progression.

Area of Science:

  • Neuroimaging
  • Neuropathology
  • Alzheimer's Disease Research

Background:

  • The amygdala, entorhinal cortex (ERC), and hippocampus are critical brain structures affected in neurodegenerative diseases.
  • Understanding the regional and temporal patterns of atrophy is crucial for early diagnosis and tracking disease progression.

Purpose of the Study:

  • To investigate the associations between atrophy in the amygdala, ERC, and hippocampus using MRI and PET.
  • To determine if atrophy in these regions precedes hippocampal atrophy and correlates with tau pathology.

Main Methods:

  • Analysis of magnetic resonance imaging (MRI) and Positron Emission Tomography (PET) scans from two independent cohorts (ADNI and BIOCARD).
  • Calculation of volume atrophy rates for amygdala, ERC, and hippocampus.
  • Laminar reconstructions and high-field atlasing for detailed regional analysis of amygdala subregions.

Main Results:

  • The amygdala, ERC, and transentorhinal cortex (TEC) exhibit earlier volume atrophy than the hippocampus.
  • ERC/TEC volume loss is associated with cortical thinning, linked to layer-specific tau pathology.
  • Medial amygdala subregions show predominant volume loss, correlating with tau PET measures and spatial co-localization of tau pathology.

Conclusions:

  • Early atrophy in the amygdala, ERC, and TEC is a key feature in Alzheimer's disease.
  • Atrophy patterns in these regions serve as potential biomarkers for disease progression and tau pathology.
  • The findings highlight the importance of medial amygdala subregions and ERC/TEC in early Alzheimer's pathology.
Keywords:
Alzheimer’s diseaseAmygdala atrophyLaminar cortical thinningMRI biomarkersMultimodal neuroimaging

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