TY - JOUR
T1 - Plasma Neurofilament Light and Alzheimer's Disease Biomarkers in Down Syndrome
T2 - Results from the Down Syndrome Biomarker Initiative (DSBI)
AU - Rafii, Michael S.
AU - Donohue, Michael C.
AU - Matthews, Dawn C.
AU - Muranevici, Gabriela
AU - Ness, Seth
AU - O'Bryant, Sid E.
AU - Rissman, Robert A.
PY - 2019
Y1 - 2019
N2 - Background: Adults with Down syndrome (DS) are at very high risk for Alzheimer's disease (AD). Neurofilament light (NF-L) has emerged as a potential blood-based biomarker of neurodegeneration due to AD. Objective: To understand the relationship between plasma NF-L with age, brain amyloid, and tau pathology, neurodegeneration as well as cognitive and functional performance. Methods: We analyzed imaging data as well as cognitive measures in relation to plasma NF-L in adults with DS, ages 30 to 60 who were enrolled in the Down Syndrome Biomarker Initiative. Results: We found significant correlations between NF-L plasma concentrations and amyloid pathology (r=0.73, p=0.007, pa=0.041) and significant inverse correlations with regional glucose metabolism in 5 of 6 regions examined, which were Anterior cingulate (r=-0.55, p=0.067, pa=0.067), Posterior cingulate r=-0.90, p<0.001, pa<0.001), Lateral Temporal (r=-0.78, p=0.004, pa=0.012), Frontal cortex (r=-0.90, p<0.001, p pa<0.001), Parietal cortex (r=-0.82, p=0.002, pa=0.008), Precuneus (r=-0.73, pa=0.010, pa=0.020), and with hippocampal volume (r=-0.52, p=0.084, pa=0.084); and an inverse correlation with direct measures of cognition: CAMCOG (r=-0.66 p=0.022, pa=0.066) and positive correlation with CANTAB Paired Associates Learning (PAL) error rate (r=0.68, p=0.015, pa=0.060). Finally, we found inverse relationships with informant-based functional measures (r=-0.57, p=0.059, pa=0.084) and OMQ-PF (r=-0.74, p=0.008, pa=0.041). Conclusion: Plasma NF-L is associated with progressive neurodegeneration as well as with declines in cognitive and functional measures in adults with DS.
AB - Background: Adults with Down syndrome (DS) are at very high risk for Alzheimer's disease (AD). Neurofilament light (NF-L) has emerged as a potential blood-based biomarker of neurodegeneration due to AD. Objective: To understand the relationship between plasma NF-L with age, brain amyloid, and tau pathology, neurodegeneration as well as cognitive and functional performance. Methods: We analyzed imaging data as well as cognitive measures in relation to plasma NF-L in adults with DS, ages 30 to 60 who were enrolled in the Down Syndrome Biomarker Initiative. Results: We found significant correlations between NF-L plasma concentrations and amyloid pathology (r=0.73, p=0.007, pa=0.041) and significant inverse correlations with regional glucose metabolism in 5 of 6 regions examined, which were Anterior cingulate (r=-0.55, p=0.067, pa=0.067), Posterior cingulate r=-0.90, p<0.001, pa<0.001), Lateral Temporal (r=-0.78, p=0.004, pa=0.012), Frontal cortex (r=-0.90, p<0.001, p pa<0.001), Parietal cortex (r=-0.82, p=0.002, pa=0.008), Precuneus (r=-0.73, pa=0.010, pa=0.020), and with hippocampal volume (r=-0.52, p=0.084, pa=0.084); and an inverse correlation with direct measures of cognition: CAMCOG (r=-0.66 p=0.022, pa=0.066) and positive correlation with CANTAB Paired Associates Learning (PAL) error rate (r=0.68, p=0.015, pa=0.060). Finally, we found inverse relationships with informant-based functional measures (r=-0.57, p=0.059, pa=0.084) and OMQ-PF (r=-0.74, p=0.008, pa=0.041). Conclusion: Plasma NF-L is associated with progressive neurodegeneration as well as with declines in cognitive and functional measures in adults with DS.
KW - Alzheimer's disease
KW - Down syndrome
KW - amyloid
KW - biomarkers
KW - blood
KW - neurofilament light
KW - plasma
KW - tau
UR - http://www.scopus.com/inward/record.url?scp=85068549415&partnerID=8YFLogxK
U2 - 10.3233/JAD-190322
DO - 10.3233/JAD-190322
M3 - Article
C2 - 31156181
AN - SCOPUS:85068549415
SN - 1387-2877
VL - 70
SP - 131
EP - 138
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
IS - 1
ER -