4.5 Article

Multimodal in vivo and postmortem assessments of tau in Lewy body disorders

Journal

NEUROBIOLOGY OF AGING
Volume 96, Issue -, Pages 137-147

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2020.08.003

Keywords

Lewy body diseases; PET imaging; Tau; CSF; Cognition; Neuropathology

Funding

  1. American Academy of Neurology/American Brain Foundation [2059]
  2. National Institutes of Health [TL1TR001880, AG010124, AG058732, AG061277, NS088341, NS053488]
  3. Alzheimer's Association [AARF-16-443681]
  4. AVID Radiopharmaceuticals

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We compared regional retention of 18F-flortaucipir between 20 patients with Lewy body disorders (LBD), 12 Alzheimer's disease patients with positive amyloid positron emission tomography (PET) scans (AD+AB) and 15 healthy controls with negative amyloid PET scans (HC-AB). In LBD subjects, we compared the relationship between F-18-flortaucipir retention and cerebrospinal fluid (CSF) tau, cognitive performance, and neuropathological tau at autopsy. The LBD cohort was stratified using an AB42 cut-off of 192 pg/mL to enrich for groups likely harboring tau pathology (LBD+AB = 11, LBD-AB = 9). 18Fflortaucipir retention was higher in LBD+AB than HC-AB in five, largely temporal-parietal regions with sparing of medial temporal regions. Higher retention was associated with higher CSF total-tau levels (p = 0.04), poorer domain-specific cognitive performance (p = 0.02-0.04), and greater severity of neuropathological tau in corresponding regions. While F-18-flortaucipir retention in LBD is intermediate between healthy controls and AD, retention relates to cognitive impairment, CSF total-tau, and neuropathological tau. Future work in larger autopsy-validated cohorts is needed to define LBD-specific tau biomarker profiles. (C) 2020 Elsevier Inc. All rights reserved.

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