Benedet Andréa L, Ashton Nicholas J, Pascoal Tharick A, Leuzy Antoine, Mathotaarachchi Sulantha, Kang Min S, Therriault Joseph, Savard Melissa, Chamoun Mira, Schöll Michael, Zimmer Eduardo R, Gauthier Serge, Labbe Aurélie, Zetterberg Henrik, Blennow Kaj, Neto Pedro R
Translational Neuroimaging Laboratory, McGill Centre for Studies in Aging, McGill University, Montreal, Quebec, Canada.
CAPES Foundation, Ministry of Education of Brazil, Brasília, Brazil.
Alzheimers Dement (Amst). 2019 Sep 27;11:679-689. doi: 10.1016/j.dadm.2019.08.002. eCollection 2019 Dec.
Neurofilament light chain (NfL) is a promising blood biomarker to detect neurodegeneration in Alzheimer's disease (AD) and other brain disorders. However, there are limited reports of how longitudinal NfL relates to imaging biomarkers. We herein investigated the relationship between blood NfL and brain metabolism in AD.
Voxelwise regression models tested the cross-sectional association between [F]fluorodeoxyglucose ([F]FDG) and both plasma and cerebrospinal fluid NfL in cognitively impaired and unimpaired subjects. Linear mixed models were also used to test the longitudinal association between NfL and [F]FDG in amyloid positive (Aβ+) and negative (Aβ-) subjects.
Higher concentrations of plasma and cerebrospinal fluid NfL were associated with reduced [F]FDG uptake in correspondent brain regions. In Aβ+ participants, NfL associates with hypometabolism in AD-vulnerable regions. Longitudinal changes in the association [F]FDG-NfL were confined to cognitively impaired Aβ+ individuals.
These findings indicate that plasma NfL is a proxy for neurodegeneration in AD-related regions in Aβ+ subjects.
神经丝轻链（NfL）是一种很有前景的血液生物标志物，可用于检测阿尔茨海默病（AD）和其他脑部疾病中的神经退行性变。然而，关于纵向NfL与成像生物标志物之间关系的报道有限。我们在此研究了AD患者血液NfL与脑代谢之间的关系。
体素回归模型测试了认知功能受损和未受损受试者中[F]氟代脱氧葡萄糖（[F]FDG）与血浆和脑脊液NfL之间的横断面关联。线性混合模型也用于测试淀粉样蛋白阳性（Aβ+）和阴性（Aβ-）受试者中NfL与[F]FDG之间的纵向关联。
血浆和脑脊液中较高浓度的NfL与相应脑区[F]FDG摄取减少有关。在Aβ+参与者中，NfL与AD易损区域的代谢减退有关。[F]FDG-NfL关联的纵向变化仅限于认知功能受损的Aβ+个体。
这些发现表明，血浆NfL是Aβ+受试者AD相关区域神经退行性变的一个指标。
