ATN incorporating cerebrospinal fluid neurofilament light chain detects frontotemporal lobar degeneration

被引：24

作者：

Cousins, Katheryn A. Q. ^{[1
]}

Phillips, Jeffrey S. ^{[1
]}

Irwin, David J. ^{[1
]}

Lee, Edward B. ^{[2
]}

Wolk, David A. ^{[2
]}

Shaw, Leslie M. ^{[2
]}

Zetterberg, Henrik ^{[3
,4
,5
,6
]}

Blennow, Kaj ^{[3
,4
]}

Burke, Sarah E. ^{[1
]}

Kinney, Nikolas G. ^{[1
]}

Gibbons, Garrett S. ^{[2
]}

McMillan, Corey T. ^{[1
]}

Trojanowski, John Q. ^{[2
]}

Grossman, Murray ^{[1
]}

机构：

[1] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA

[2] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA USA

[3] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Gothenburg, Sweden

[4] Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden

[5] UCL, Inst Neurol, Dept Neurodegenerat Dis, London, England

[6] UCL, UK Dementia Res Inst, London, England

来源：

ALZHEIMERS & DEMENTIA | 2021年 / 17卷 / 05期

基金：

英国医学研究理事会;

关键词：

Alzheimer' s disease; ATN; biomarkers; cerebrospinal fluid; frontotemporal degeneration; neurofilament light chain; suspected non‐ s pathophysiology; total tau; ALZHEIMERS-DISEASE; CSF BIOMARKERS; TAU PATHOLOGY; DEMENTIA; SEVERITY; BRAIN; AD; ASSOCIATION; PROGRESSION; SIGNATURE;

D O I：

10.1002/alz.12233

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Introduction The ATN framework provides an in vivo diagnosis of Alzheimer's disease (AD) using cerebrospinal fluid (CSF) biomarkers of pathologic amyloid plaques (A), tangles (T), and neurodegeneration (N). ATN is rarely evaluated in pathologically confirmed patients and its poor sensitivity to suspected non-Alzheimer's pathophysiologies (SNAP), including frontotemporal lobar degeneration (FTLD), leads to misdiagnoses. We compared accuracy of ATN (ATN(TAU)) using CSF total tau (t-tau) to a modified strategy (ATN(NfL)) using CSF neurofilament light chain (NfL) in an autopsy cohort. Methods ATN(TAU) and ATN(NfL) were trained in an independent sample and validated in autopsy-confirmed AD (n = 67) and FTLD (n = 27). Results ATN(NfL) more accurately identified FTLD as SNAP (sensitivity = 0.93, specificity = 0.94) than ATN(TAU) (sensitivity = 0.44, specificity = 0.97), even in cases with co-occurring AD and FTLD. ATN(NfL) misclassified fewer AD and FTLD as "Normal" (2%) than ATN(TAU) (14%). Discussion ATN(NfL) is a promising diagnostic strategy that may accurately identify both AD and FTLD, even when pathologies co-occur.

引用

页码：822 / 830

页数：9

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