Cousins, KAQ;
Phillips, JS;
Irwin, DJ;
Lee, EB;
Wolk, DA;
Shaw, LM;
Zetterberg, H;
... Grossman, M; + view all
(2021)
ATN incorporating cerebrospinal fluid neurofilament light chain detects frontotemporal lobar degeneration.
Alzheimer's & Dementia
, 17
(5)
pp. 822-830.
10.1002/alz.12233.
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Zetterberg_ATN incorporating cerebrospinal fluid neurofilament light chain detects frontotemporal lobar degeneration_AAM.pdf - Accepted Version Download (1MB) | Preview |
Abstract
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 (ATNTAU ) using CSF total tau (t-tau) to a modified strategy (ATNNfL ) using CSF neurofilament light chain (NfL) in an autopsy cohort. METHODS: ATNTAU and ATNNfL were trained in an independent sample and validated in autopsy-confirmed AD (n = 67) and FTLD (n = 27). RESULTS: ATNNfL more accurately identified FTLD as SNAP (sensitivity = 0.93, specificity = 0.94) than ATNTAU (sensitivity = 0.44, specificity = 0.97), even in cases with co-occurring AD and FTLD. ATNNfL misclassified fewer AD and FTLD as "Normal" (2%) than ATNTAU (14%). DISCUSSION: ATNNfL is a promising diagnostic strategy that may accurately identify both AD and FTLD, even when pathologies co-occur.
| Type: | Article |
|---|---|
| Title: | ATN incorporating cerebrospinal fluid neurofilament light chain detects frontotemporal lobar degeneration |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/alz.12233 |
| Publisher version: | https://doi.org/10.1002/alz.12233 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions. |
| Keywords: | ATN, Alzheimer's disease, biomarkers, cerebrospinal fluid, frontotemporal degeneration, neurofilament light chain, suspected non-Alzheimer's pathophysiology, total tau |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10118879 |
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