T1 and FLAIR signal intensities are related to tau pathology in dominantly inherited Alzheimer disease

Farzaneh Rahmani, Matthew R. Brier, Brian A. Gordon, Nicole McKay, Shaney Flores, Sarah Keefe, Russ Hornbeck, Beau Ances, Nelly Joseph-Mathurin, Chengjie Xiong, Guoqiao Wang, Cyrus A. Raji, Jorge J. Libre-Guerra, Richard J. Perrin, Eric McDade, Alisha Daniels, Celeste Karch, Gregory S. Day, Adam M. Brickman, Michael FulhamClifford R. Jack, Christian la La Fougère, Gerald Reischl, Peter R. Schofield, Hwamee Oh, Johannes Levin, Jonathan Vöglein, David M. Cash, Igor Yakushev, Takeshi Ikeuchi, William E. Klunk, John C. Morris, Randall J. Bateman, Tammie L.S. Benzinger

Research output: Contribution to journalArticlepeer-review


Carriers of mutations responsible for dominantly inherited Alzheimer disease provide a unique opportunity to study potential imaging biomarkers. Biomarkers based on routinely acquired clinical MR images, could supplement the extant invasive or logistically challenging) biomarker studies. We used 1104 longitudinal MR, 324 amyloid beta, and 87 tau positron emission tomography imaging sessions from 525 participants enrolled in the Dominantly Inherited Alzheimer Network Observational Study to extract novel imaging metrics representing the mean (μ) and standard deviation (σ) of standardized image intensities of T1-weighted and Fluid attenuated inversion recovery (FLAIR) MR scans. There was an exponential decrease in FLAIR-μ in mutation carriers and an increase in FLAIR and T1 signal heterogeneity (T1-σ and FLAIR-σ) as participants approached the symptom onset in both supramarginal, the right postcentral and right superior temporal gyri as well as both caudate nuclei, putamina, thalami, and amygdalae. After controlling for the effect of regional atrophy, FLAIR-μ decreased and T1-σ and FLAIR-σ increased with increasing amyloid beta and tau deposition in numerous cortical regions. In symptomatic mutation carriers and independent of the effect of regional atrophy, tau pathology demonstrated a stronger relationship with image intensity metrics, compared with amyloid pathology. We propose novel MR imaging intensity-based metrics using standard clinical T1 and FLAIR images which strongly associates with the progression of pathology in dominantly inherited Alzheimer disease. We suggest that tau pathology may be a key driver of the observed changes in this cohort of patients.

Original languageEnglish
Pages (from-to)6375-6387
Number of pages13
JournalHuman Brain Mapping
Issue number18
StatePublished - Dec 15 2023


  • T1 and FLAIR signal intensity
  • amyloid PET
  • dominantly inherited Alzheimer disease
  • quantitative MR imaging
  • tau PET


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