Magnetic resonance evidence of increased iron content in subcortical brain regions in asymptomatic Alzheimer's disease

• Type of Material: Article
• Authors: Qixiang Lin, Emory University; Salman Shahid, Emory University; Antonie Hone-Blanchet, Emory University; Shuai Huang, Emory University; Junjie Wu, Emory University; Aditya Bisht, Emory University; David Loring, Emory University; Felicia Goldstein, Emory University; Allan Levey, Emory University; Bruce Crosson, Emory University; James Lah, Emory University; Deqiang Qiu, Emory University
• Language: English
• Date: 2023-03-16
• Publisher: WILEY
• Publication Version: Final Published Version
• Copyright Statement: © 2023 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1002/hbm.26263
• Title of Journal or Parent Work: HUMAN BRAIN MAPPING
• Volume: 44
• Issue: 8
• Start Page: 3072
• End Page: 3083
• Keywords: Science & Technology; Alzheimer's disease; Radiology, Nuclear Medicine & Medical Imaging; BASAL GANGLIA; aging; BURDEN; CEREBROSPINAL-FLUID; NEURODEGENERATION; PATHOLOGY; subcortical; AMYLOID-BETA; quantitative magnetic resonance imaging; Neuroimaging; COGNITIVE DECLINE; grey matter; iron deposition; Neurosciences & Neurology; TRANSVERSE RELAXATION RATES; AGE-RELATED DIFFERENCES; Neurosciences; GRAY-MATTER; beta-amyloid; Life Sciences & Biomedicine
• Research Categories: Health Sciences, Radiology; Engineering, Biomedical

Abstract

While iron over-accumulation has been reported in late stage Alzheimer's disease (AD), whether this occurs early in the asymptomatic stage of AD remains unknown. We aimed to assess brain iron levels in asymptomatic AD using quantitative MR relaxometry of effective transverse relaxation rate (R2*) and longitudinal relaxation rate (R1), and recruited 118 participants comprised of three groups including healthy young participants, and cognitively normal older individuals without or with positive AD biomarkers based on cerebrospinal fluid (CSF) proteomics analysis. Compared with the healthy young group, increased R2* was found in widespread cortical and subcortical regions in the older groups. Further, significantly higher levels of R2* were found in the cognitively normal older subjects with positive CSF AD biomarker (i.e., asymptomatic AD) compared with those with negative AD biomarker in subcortical regions including the left and right caudate, left and right putamen, and left and right globus pallidus (p <.05 for all regions), suggesting increased iron content in these regions. Subcortical R2* of some regions was found to significantly correlate with CSF AD biomarkers and neuropsychological assessments of visuospatial functions. In conclusion, R2* could be a valuable biomarker for studying early pathophysiological changes in AD.