Plasma Neurofilament Light and Alzheimer's Disease Biomarkers in Down Syndrome: Results from the Down Syndrome Biomarker Initiative (DSBI)

Michael S. Rafii, Michael C. Donohue, Dawn C. Matthews, Gabriela Muranevici, Seth Ness, Sidney O'Bryant, Robert A. Rissman

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)131-138
Number of pages8
JournalJournal of Alzheimer's Disease
Volume70
Issue number1
DOIs
StatePublished - 1 Jan 2019

Fingerprint

Intermediate Filaments
Down Syndrome
Alzheimer Disease
Biomarkers
Light
Parietal Lobe
Gyrus Cinguli
Amyloid
Paired-Associate Learning
Pathology
Frontal Lobe
Cognition
Glucose
Brain

Keywords

  • Alzheimer's disease
  • Down syndrome
  • amyloid
  • biomarkers
  • blood
  • neurofilament light
  • plasma
  • tau

Cite this

Rafii, Michael S. ; Donohue, Michael C. ; Matthews, Dawn C. ; Muranevici, Gabriela ; Ness, Seth ; O'Bryant, Sidney ; Rissman, Robert A. / Plasma Neurofilament Light and Alzheimer's Disease Biomarkers in Down Syndrome : Results from the Down Syndrome Biomarker Initiative (DSBI). In: Journal of Alzheimer's Disease. 2019 ; Vol. 70, No. 1. pp. 131-138.
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title = "Plasma Neurofilament Light and Alzheimer's Disease Biomarkers in Down Syndrome: Results from the Down Syndrome Biomarker Initiative (DSBI)",
abstract = "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.",
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Plasma Neurofilament Light and Alzheimer's Disease Biomarkers in Down Syndrome : Results from the Down Syndrome Biomarker Initiative (DSBI). / Rafii, Michael S.; Donohue, Michael C.; Matthews, Dawn C.; Muranevici, Gabriela; Ness, Seth; O'Bryant, Sidney; Rissman, Robert A.

In: Journal of Alzheimer's Disease, Vol. 70, No. 1, 01.01.2019, p. 131-138.

Research output: Contribution to journalArticle

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, Sidney

AU - Rissman, Robert A.

PY - 2019/1/1

Y1 - 2019/1/1

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

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