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ATN incorporating cerebrospinal fluid neurofilament light chain detects frontotemporal lobar degeneration
Author(s) -
Cousins Katheryn A.Q.,
Phillips Jeffrey S.,
Irwin David J.,
Lee Edward B.,
Wolk David A.,
Shaw Leslie M.,
Zetterberg Henrik,
Blennow Kaj,
Burke Sarah E.,
Kinney Nikolas G.,
Gibbons Garrett S.,
McMillan Corey T.,
Trojanowski John Q.,
Grossman Murray
Publication year - 2021
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.12233
Subject(s) - frontotemporal lobar degeneration , pathology , cerebrospinal fluid , neurodegeneration , autopsy , medicine , alzheimer's disease , neurofilament , frontotemporal dementia , atrophy , dementia , disease , immunohistochemistry
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 (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.