Multimodal In Vivo and Post-mortem Assessments of Tau in Lewy Body Disorders,Neurobiology of Aging

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Multimodal In Vivo and Post-mortem Assessments of Tau in Lewy Body Disorders
Neurobiology of Aging ( IF 4.2 ) Pub Date : 2020-12-01 , DOI: 10.1016/j.neurobiolaging.2020.08.003
David G Coughlin ₁ , Jeffrey S Phillips ₂ , Emily Roll ₂ , Claire Peterson ₃ , Rebecca Lobrovich ₃ , Katya Rascovsky ₂ , Molly Ungrady ₂ , David A Wolk ₄ , Sandhitsu Das ₄ , Daniel Weintraub ₅ , Edward B Lee ₆ , John Q Trojanowski ₇ , Leslie M Shaw ₈ , Sanjeev Vaishnavi ₉ , Andrew Siderowf ₉ , Ilya M Nasrallah ₁₀ , David J Irwin ₁₁ , Corey T McMillan ₂ ,

Affiliation

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.
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.
Digital Neuropathology Laboratory, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
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 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.
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.
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.
Department of Pathology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
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.
Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
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.

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.

中文翻译：

路易体疾病中 Tau 的多模态体内和死后评估

我们比较了 20 名路易体病 (LBD) 患者、12 名淀粉样蛋白正电子发射断层扫描 (PET) 阳性的阿尔茨海默病患者 (AD+Aβ) 和 15 名淀粉样蛋白 PET 扫描阴性的健康对照者 (HC- Aβ）。在 LBD 受试者中，我们比较了尸检时 18F-flortaucipir 滞留与脑脊液 (CSF) tau、认知表现和神经病理学 tau 之间的关系。使用 192 pg/mL 的 Aβ42 截止值对 LBD 队列进行分层，以丰富可能携带 tau 病理学的群体（LBD+Aβ = 11，LBD-Aβ = 9）。LBD+AB 中的 18F-flortaucipir 保留在五个主要是颞顶叶区域的 LBD+AB 中高于 HC-Aβ，内侧颞叶区域保留。更高的保留与更高的 CSF 总 tau 水平相关（p = 0.04），较差的特定领域认知表现 (p = 0.02-0.04)，以及相应区域神经病理学 tau 的严重程度。虽然 LBD 中的 18F-flortaucipir 滞留介于健康对照和 AD 之间，但滞留与认知障碍、CSF 总 tau 和神经病理性 tau 相关。未来需要在更大的尸检验证队列中开展工作，以定义 LBD 特异性 tau 生物标志物概况。

更新日期：2020-12-01

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