The Sporadic Early-onset Alzheimer's Disease Signature Of Atrophy: Preliminary Findings From The Longitudinal Early-onset Alzheimer's Disease Study (LEADS) Cohort

Alexandra Touroutoglou, Yuta Katsumi, Michael Brickhouse, Alexander Zaitsev, Ryan Eckbo, Paul Aisen, Laurel Beckett, Jeffrey L. Dage, Ani Eloyan, Tatiana Foroud, Bernardino Ghetti, Percy Griffin, Dustin Hammers, Clifford R. Jack, Joel H. Kramer, Leonardo Iaccarino, Renaud La Joie, Nidhi S. Mundada, Robert Koeppe, Walter A. KukullMelissa E. Murray, Kelly Nudelman, Angelina J. Polsinelli, Malia Rumbaugh, David N. Soleimani-Meigooni, Arthur Toga, Prashanthi Vemuri, Alireza Atri, Gregory S. Day, Ranjan Duara, Neill R. Graff-Radford, Lawrence S. Honig, David T. Jones, Joseph C. Masdeu, Mario F. Mendez, Erik Musiek, Chiadi U. Onyike, Meghan Riddle, Emily Rogalski, Stephen Salloway, Sharon Sha, R. Scott Turner, Thomas S. Wingo, David A. Wolk, Kyle Womack, Maria C. Carrillo, Gil D. Rabinovici, Liana G. Apostolova, Bradford C. Dickerson

Research output: Contribution to journalReview articlepeer-review

2 Scopus citations

Abstract

INTRODUCTION: Magnetic resonance imaging (MRI) research has advanced our understanding of neurodegeneration in sporadic early-onset Alzheimer's disease (EOAD) but studies include small samples, mostly amnestic EOAD, and have not focused on developing an MRI biomarker. METHODS: We analyzed MRI scans to define the sporadic EOAD-signature atrophy in a small sample (n = 25) of Massachusetts General Hospital (MGH) EOAD patients, investigated its reproducibility in the large longitudinal early-onset Alzheimer's disease study (LEADS) sample (n = 211), and investigated the relationship of the magnitude of atrophy with cognitive impairment. RESULTS: The EOAD-signature atrophy was replicated across the two cohorts, with prominent atrophy in the caudal lateral temporal cortex, inferior parietal lobule, and posterior cingulate and precuneus cortices, and with relative sparing of the medial temporal lobe. The magnitude of EOAD-signature atrophy was associated with the severity of cognitive impairment. DISCUSSION: The EOAD-signature atrophy is a reliable and clinically valid biomarker of AD-related neurodegeneration that could be used in clinical trials for EOAD. Highlights: We developed an early-onset Alzheimer's disease (EOAD)–signature of atrophy based on magnetic resonance imaging (MRI) scans. EOAD signature was robustly reproducible across two independent patient cohorts. EOAD signature included prominent atrophy in parietal and posterior temporal cortex. The EOAD-signature atrophy was associated with the severity of cognitive impairment. EOAD signature is a reliable and clinically valid biomarker of neurodegeneration.

Original languageEnglish (US)
Pages (from-to)S74-S88
JournalAlzheimer's and Dementia
Volume19
Issue numberS9
DOIs
StatePublished - Nov 2023

Keywords

  • disease signature
  • early-onset Alzheimer's disease
  • magnetic resonance imaging (MRI)

ASJC Scopus subject areas

  • Epidemiology
  • Health Policy
  • Developmental Neuroscience
  • Clinical Neurology
  • Geriatrics and Gerontology
  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health

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