William Charles Kreisl1,2, Patrick J Lao1,2, Aubrey Johnson1,2, Zeljko Tomljanovic1,2, Julia Klein1,2, Krista Polly1,2, Benjamin Maas1,2, Krystal K Laing1,2, Anthony G Chesebro1,2, Kay Igwe1,2, Qolamreza R Razlighi3, Lawrence S Honig1,2, Xinyu Yan4, Seonjoo Lee4,5, Akiva Mintz6, José A Luchsinger7,8, Yaakov Stern1,2, D P Devanand9,10, Adam M Brickman1,2. 1. Department of Neurology, Columbia University Irving Medical Center, New York, NY, USA. 2. Taub Institute for Research on Alzheimer's Disease and the Aging Brain, New York, NY, USA. 3. Department of Radiology, Weill Cornell Medicine, New York, NY, USA. 4. Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY, USA. 5. Division of Mental Health Data Science, New York State Psychiatric Institute, New York, NY, USA. 6. Department of Radiology, Columbia University Irving Medical Center, New York, NY, USA. 7. Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA. 8. Department of Epidemiology, Mailman School of Public Health, Columbia University Irving Medical Center, New York, NY, USA. 9. Department of Psychiatry, Columbia University Irving Medical Center, New York, NY, USA. 10. Division of Geriatric Psychiatry, New York State Psychiatric Institute, New York, NY, USA.
Abstract
INTRODUCTION: Positron emission tomography (PET) imaging for neurofibrillary tau allows investigation of the in vivo spatiotemporal progression of Alzheimer's disease (AD) pathology. We evaluated the suitability of 18 F-MK-6240 in a clinical sample and determined the relationships among 18 F-MK-6240 binding, age, cognition, and cerebrospinal fluid (CSF)-based AD biomarkers. METHODS: Participants (n = 101, 72 ± 9 years, 52% women) underwent amyloid PET, tau PET, structural T1-weighted magnetic resonance imaging, and neuropsychological evaluation. Twenty-one participants had lumbar puncture for CSF measurement of amyloid beta (Aβ)42 , tau, and phosphorylated tau (p-tau). RESULTS: 18 F-MK-6240 recapitulated Braak staging and correlated with CSF tau and p-tau, normalized to Aβ42 . 18 F-MK-6240 negatively correlated with age across Braak regions in amyloid-positive participants, consistent with greater tau pathology in earlier onset AD. Domain-specific, regional patterns of 18 F-MK-6240 binding were associated with reduced memory, executive, and language performance, but only in amyloid-positive participants. DISCUSSION: 18 F-MK-6240 can approximate Braak staging across the AD continuum and provide region-dependent insights into biomarker-based AD models.
INTRODUCTION: Positron emission tomography (PET) imaging for neurofibrillary tau allows investigation of the in vivo spatiotemporal progression of Alzheimer's disease (AD) pathology. We evaluated the suitability of 18 F-MK-6240 in a clinical sample and determined the relationships among 18 F-MK-6240 binding, age, cognition, and cerebrospinal fluid (CSF)-based AD biomarkers. METHODS: Participants (n = 101, 72 ± 9 years, 52% women) underwent amyloid PET, tau PET, structural T1-weighted magnetic resonance imaging, and neuropsychological evaluation. Twenty-one participants had lumbar puncture for CSF measurement of amyloid beta (Aβ)42 , tau, and phosphorylated tau (p-tau). RESULTS: 18 F-MK-6240 recapitulated Braak staging and correlated with CSF tau and p-tau, normalized to Aβ42 . 18 F-MK-6240 negatively correlated with age across Braak regions in amyloid-positive participants, consistent with greater tau pathology in earlier onset AD. Domain-specific, regional patterns of 18 F-MK-6240 binding were associated with reduced memory, executive, and language performance, but only in amyloid-positive participants. DISCUSSION: 18 F-MK-6240 can approximate Braak staging across the AD continuum and provide region-dependent insights into biomarker-based AD models.
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