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Association of cerebrospinal fluid neurofilament light concentration with Alzheimer disease progression

Zetterberg, Henrik LU ; Skillbäck, Tobias; Mattsson, Niklas LU ; Trojanowski, John Q.; Portelius, Erik; Shaw, Leslie M.; Weiner, Michael W. and Blennow, Kaj LU (2016) In JAMA Neurology 73(1). p.60-67
Abstract

IMPORTANCE The extent to which large-caliber axonal degeneration contributes to Alzheimer disease (AD) progression is unknown. Cerebrospinal fluid (CSF) neurofilament light (NFL) concentration is a general marker of damage to large-calibermyelinated axons. OBJECTIVE To test whether CSF NFL concentration is associated with cognitive decline and imaging evidence of neurodegeneration and white matter change in AD. DESIGN, SETTING, AND PARTICIPANTS A commercially available immunoassaywas used to analyze CSF NFL concentration in a cohort of patients with AD (n = 95) or mild cognitive impairment (MCI) (n = 192) and in cognitively normal individuals (n = 110) from the Alzheimer's Disease Neuroimaging Initiative. The study dates were January... (More)

IMPORTANCE The extent to which large-caliber axonal degeneration contributes to Alzheimer disease (AD) progression is unknown. Cerebrospinal fluid (CSF) neurofilament light (NFL) concentration is a general marker of damage to large-calibermyelinated axons. OBJECTIVE To test whether CSF NFL concentration is associated with cognitive decline and imaging evidence of neurodegeneration and white matter change in AD. DESIGN, SETTING, AND PARTICIPANTS A commercially available immunoassaywas used to analyze CSF NFL concentration in a cohort of patients with AD (n = 95) or mild cognitive impairment (MCI) (n = 192) and in cognitively normal individuals (n = 110) from the Alzheimer's Disease Neuroimaging Initiative. The study dates were January 2005 to December 2007. The NFL analysis was performed in November 2014. MAIN OUTCOMES AND MEASURES Correlationwas investigated among baseline CSF NFL concentration and longitudinal cognitive impairment, white matter change, and regional brain atrophy within each diagnostic group. RESULTS Cerebrospinal fluid NFL concentration (median [interquartile range]) was higher in the AD dementia group (1479 [1134-1842] pg/mL), stable MCI group (no progression to AD during follow-up; 1182 [923-1687] pg/mL), and progressive MCI group (MCI with progression to AD dementia during follow-up; 1336 [1061-1693] pg/mL) compared with control participants (1047 [809-1265] pg/mL) (P < .001 for all) and in the AD dementia group compared with the stable MCI group (P = .01). In the MCI group, a higher CSF NFL concentration was associated with faster brain atrophy over time as measured by changes in whole-brain volume (ß = -4177, P = .003), ventricular volume (ß = 1835, P < .001), and hippocampus volume (ß = -54.22, P < .001); faster disease progression as reflected by decreased Mini-Mental State Examination scores (ß = -1.077, P < .001) and increased Alzheimer Disease Assessment Scale cognitive subscale scores (ß = 2.30, P < .001); and faster white matter intensity change (ß = 598.7, P < .001). CONCLUSIONS AND RELEVANCE Cerebrospinal fluid NFL concentration is increased by the early clinical stage of AD and is associated with cognitive deterioration and structural brain changes over time. This finding corroborates the contention that degeneration of large-caliber axons is an important feature of AD neurodegeneration.

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organization
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type
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published
subject
in
JAMA Neurology
volume
73
issue
1
pages
8 pages
publisher
American Medical Association
external identifiers
  • scopus:84954224391
ISSN
2168-6149
DOI
10.1001/jamaneurol.2015.3037
language
English
LU publication?
yes
id
b9d5f1ea-8f63-4e7d-bd11-3c202f3beaa9
date added to LUP
2019-02-01 14:46:30
date last changed
2019-05-21 04:18:16
@article{b9d5f1ea-8f63-4e7d-bd11-3c202f3beaa9,
  abstract     = {<p>IMPORTANCE The extent to which large-caliber axonal degeneration contributes to Alzheimer disease (AD) progression is unknown. Cerebrospinal fluid (CSF) neurofilament light (NFL) concentration is a general marker of damage to large-calibermyelinated axons. OBJECTIVE To test whether CSF NFL concentration is associated with cognitive decline and imaging evidence of neurodegeneration and white matter change in AD. DESIGN, SETTING, AND PARTICIPANTS A commercially available immunoassaywas used to analyze CSF NFL concentration in a cohort of patients with AD (n = 95) or mild cognitive impairment (MCI) (n = 192) and in cognitively normal individuals (n = 110) from the Alzheimer's Disease Neuroimaging Initiative. The study dates were January 2005 to December 2007. The NFL analysis was performed in November 2014. MAIN OUTCOMES AND MEASURES Correlationwas investigated among baseline CSF NFL concentration and longitudinal cognitive impairment, white matter change, and regional brain atrophy within each diagnostic group. RESULTS Cerebrospinal fluid NFL concentration (median [interquartile range]) was higher in the AD dementia group (1479 [1134-1842] pg/mL), stable MCI group (no progression to AD during follow-up; 1182 [923-1687] pg/mL), and progressive MCI group (MCI with progression to AD dementia during follow-up; 1336 [1061-1693] pg/mL) compared with control participants (1047 [809-1265] pg/mL) (P &lt; .001 for all) and in the AD dementia group compared with the stable MCI group (P = .01). In the MCI group, a higher CSF NFL concentration was associated with faster brain atrophy over time as measured by changes in whole-brain volume (ß = -4177, P = .003), ventricular volume (ß = 1835, P &lt; .001), and hippocampus volume (ß = -54.22, P &lt; .001); faster disease progression as reflected by decreased Mini-Mental State Examination scores (ß = -1.077, P &lt; .001) and increased Alzheimer Disease Assessment Scale cognitive subscale scores (ß = 2.30, P &lt; .001); and faster white matter intensity change (ß = 598.7, P &lt; .001). CONCLUSIONS AND RELEVANCE Cerebrospinal fluid NFL concentration is increased by the early clinical stage of AD and is associated with cognitive deterioration and structural brain changes over time. This finding corroborates the contention that degeneration of large-caliber axons is an important feature of AD neurodegeneration.</p>},
  author       = {Zetterberg, Henrik and Skillbäck, Tobias and Mattsson, Niklas and Trojanowski, John Q. and Portelius, Erik and Shaw, Leslie M. and Weiner, Michael W. and Blennow, Kaj},
  issn         = {2168-6149},
  language     = {eng},
  month        = {01},
  number       = {1},
  pages        = {60--67},
  publisher    = {American Medical Association},
  series       = {JAMA Neurology},
  title        = {Association of cerebrospinal fluid neurofilament light concentration with Alzheimer disease progression},
  url          = {http://dx.doi.org/10.1001/jamaneurol.2015.3037},
  volume       = {73},
  year         = {2016},
}