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Multicenter Study
. 2023 Dec 11;24(24):17361.
doi: 10.3390/ijms242417361.

Blood Neurofilament Levels Predict Cognitive Decline across the Alzheimer's Disease Continuum

Sylvain Lehmann  1 , Susanna Schraen-Maschke  2 , Jean-Sébastien Vidal  3 , Frédéric Blanc  4 , Claire Paquet  5 , Bernadette Allinquant  6 , Stéphanie Bombois  2   7 , Audrey Gabelle  8 , Constance Delaby  1   9 , Olivier Hanon  3 ; BALTAZAR Study Group
Affiliations
Multicenter Study

Blood Neurofilament Levels Predict Cognitive Decline across the Alzheimer's Disease Continuum

Sylvain Lehmann et al. Int J Mol Sci. .

Abstract

Neurofilament light chain (NfL) is a potential diagnostic and prognostic plasma biomarker for numerous neurological diseases including Alzheimer's disease (AD). In this study, we investigated the relationship between baseline plasma concentration of Nfl and Mild Cognitive Impairment in participants who did and did not have a clinically determined diagnosis of dementia by the end of the three-year study. Additionally, we explored the connection between baseline plasma concentration of NfL and AD dementia patients, considering their demographics, clinical features, and cognitive profiles. A total of 350 participants from the Biomarker of AmyLoid pepTide and AlZheimer's diseAse Risk (BALTAZAR) multicenter prospective study were investigated: 161 AD dementia participants and 189 MCI participants (of which 141 had amnestic MCI and 48 non-amnestic MCI). Plasma biomarkers were measured at baseline and the progression of clinical and cognitive profiles was followed over the three years of follow-up. Baseline plasma NfL concentration increased across the Alzheimer's disease continuum with a mean NfL value of 17.1 ng/mL [SD = 6.1] in non-amnestic MCI, 20.7 ng/mL [SD = 12.0] in amnestic MCI, and 23.1 ng/mL [SD = 22.7] in AD dementia patients. Plasma NfL concentration correlated with age, body mass index (BMI), and global cognitive performance and decline, as measured by the Mini-Mental State Examination (MMSE). MMSE scores decreased in parallel with increasing plasma NfL concentration, independently of age and BMI. However, NfL concentration did not predict MCI participants' conversion to dementia within three years. Discussion: Baseline plasma NfL concentration is associated with cognitive status along the AD continuum, suggesting its usefulness as a potential informative biomarker for cognitive decline follow-up in patients.

Keywords: Alzheimer’s disease; blood; cognitive decline; neurofilament light chain.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Baseline plasma NfL concentration (+/− SD) in the 350 patients as per clinical diagnosis of AD dementia, aMCI, and naMCI. NfL levels at baseline were measured in 161 AD dementia patients and 189 MCI participants, of which 141 were aMCI and 48 were naMCI. The p-value of the AD vs. naMCI comparison was obtained after log transformation of the data. The comparison using non-parametric Mann–Whitney test resulted in a p-value of 0.0289 between AD and naMCI and a p-value of 0.0551 between aMCI and naMCI.
Figure 2
Figure 2
MMSE rate of variation in the different NfL tertiles. Plot showing MMSE variation over three years for the 350 participants according to plasma NfL tertile.
Figure 3
Figure 3
Baseline plasma NfL concentration and amyloid ratio prediction of conversion to dementia. Conversion occurrence amongst 189 MCI subjects according to tertile of (A) NfL and (B) amyloid ratio. NfL: logRank test: X2: 3.0068, p = 0.22; amyloid ratio logRank test: X2: 9.7546, p = 0.0076.
See this image and copyright information in PMC

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