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

David G Coughlin; Jeffrey S Phillips; Emily Roll; Claire Peterson; Rebecca Lobrovich; Katya Rascovsky; Molly Ungrady; David A Wolk; Sandhitsu Das; Daniel Weintraub; Edward B Lee; John Q Trojanowski; Leslie M Shaw; Sanjeev Vaishnavi; Andrew Siderowf; Ilya M Nasrallah; David J Irwin; Corey T McMillan; Alzheimer’s Disease Neuroimaging Initiative

doi:10.1016/j.neurobiolaging.2020.08.003

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

Neurobiol Aging. 2020 Dec:96:137-147. doi: 10.1016/j.neurobiolaging.2020.08.003. Epub 2020 Aug 21.

Authors

David G Coughlin¹, Jeffrey S Phillips², Emily Roll², Claire Peterson³, Rebecca Lobrovich³, Katya Rascovsky², Molly Ungrady², David A Wolk⁴, Sandhitsu Das⁴, Daniel Weintraub⁵, Edward B Lee⁶, John Q Trojanowski⁷, Leslie M Shaw⁸, Sanjeev Vaishnavi⁹, Andrew Siderowf⁹, Ilya M Nasrallah¹⁰, David J Irwin¹¹, Corey T McMillan¹²; Alzheimer’s Disease Neuroimaging Initiative

Affiliations

¹ Department of Neurology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA; Digital Neuropathology Laboratory, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Lewy Body Disease Center of Excellence, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
² Department of Neurology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA; Frontotemporal Degeneration Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
³ Digital Neuropathology Laboratory, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
⁴ Department of Neurology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA; Alzheimer's Disease Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
⁵ Department of Neurology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA; Michael J. Crescenz VA Medical Center, Parkinson's Disease Research, Education, and Clinical Center, Philadelphia, PA, USA.
⁶ Alzheimer's Disease Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Department of Pathology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
⁷ Department of Neurology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA; Alzheimer's Disease Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Department of Pathology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA; Center for Neurodegenerative Disease Research, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
⁸ Department of Pathology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
⁹ Department of Neurology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA; Lewy Body Disease Center of Excellence, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
¹⁰ Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
¹¹ Department of Neurology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA; Digital Neuropathology Laboratory, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Lewy Body Disease Center of Excellence, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Frontotemporal Degeneration Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
¹² Department of Neurology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA; Frontotemporal Degeneration Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. Electronic address: mcmillac@pennmedicine.upenn.edu.

PMID: 33002767
PMCID: PMC7819484
DOI: 10.1016/j.neurobiolaging.2020.08.003

Abstract

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+Aβ) and 15 healthy controls with negative amyloid PET scans (HC-Aβ). In LBD subjects, we compared the relationship between ¹⁸F-flortaucipir retention and cerebrospinal fluid (CSF) tau, cognitive performance, and neuropathological tau at autopsy. The LBD cohort was stratified using an Aβ42 cut-off of 192 pg/mL to enrich for groups likely harboring tau pathology (LBD+Aβ = 11, LBD-Aβ = 9). ¹⁸F-flortaucipir retention was higher in LBD+AB than HC-Aβ 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 ¹⁸F-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.

Keywords: CSF; Cognition; Lewy body diseases; Neuropathology; PET imaging; Tau.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Alzheimer Disease / cerebrospinal fluid
Alzheimer Disease / diagnostic imaging
Alzheimer Disease / pathology
Alzheimer Disease / psychology
Autopsy
Biomarkers / cerebrospinal fluid
Carbolines
Cognition
Female
Humans
Lewy Body Disease / cerebrospinal fluid*
Lewy Body Disease / diagnostic imaging
Lewy Body Disease / pathology
Lewy Body Disease / psychology
Male
Positron-Emission Tomography
Severity of Illness Index
tau Proteins / cerebrospinal fluid*

Substances

Biomarkers
Carbolines
tau Proteins
7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole

Abstract

Publication types

MeSH terms

Substances

Grants and funding