TY - JOUR
T1 - Cerebrospinal fluid dynamics and discordant amyloid biomarkers
AU - Graff-Radford, Jonathan
AU - Jones, David T.
AU - Wiste, Heather J.
AU - Cogswell, Petrice M.
AU - Weigand, Stephen D.
AU - Lowe, Val
AU - Elder, Benjamin D.
AU - Vemuri, Prashanthi
AU - Van Harten, Argonde
AU - Mielke, Michelle M.
AU - Knopman, David S.
AU - Graff-Radford, Neill R.
AU - Petersen, Ronald C.
AU - Jack, Clifford R.
AU - Gunter, Jeffrey L.
N1 - Funding Information:
This work was supported the National Institute on Aging (K76 AG057015, RF1 AG069052-01A1, R37 AG011378, R01 AG041851, U01 AG006786, and P50 AG016574), the National Institute of Neurologic Disorders and Stroke (NS097495), the Elsie and Marvin Dekelboum Family Foundation, the Alexander Family Professor of Alzheimer's Disease Research - Mayo Clinic, the Liston Award, the Schuler Foundation, the GHR Foundation, and the Mayo Foundation for Medical Education and Research. This study was made possible using the resources of the Rochester Epidemiology Project, which is supported by the National Institute on Aging of the National Institutes of Health under Award Number R01AG034676. The funders had no role in the preparation of this article.
Publisher Copyright:
© 2021
PY - 2022/2
Y1 - 2022/2
N2 - Do MRI-based metrics of a CSF-dynamics disorder, disproportionately enlarged subarachnoid-space hydrocephalus (DESH), correlate with discordant amyloid biomarkers (low CSF β-amyloid 1–42, normal Aβ-PET scan)? Individuals ≥50 years from the Mayo Clinic Study of Aging, with MRI, 11C-Pittsburgh compound B (Aβ) PET scans, and CSF phosphorylated-tau protein and Aβ42, were categorized into 4 groups: normal and/or abnormal by CSF β-amyloid 1–42 and Aβ amyloid PET. Within groups, we noted MRI patterns of CSF-dynamics disorders and Aβ-PET accumulation-change rate. One-hundred participants (21%) in the abnormal-CSF and/or normal-PET group had highest DESH-pattern scores and lowest CSF-phosphorylated-tau levels. Among normal amyloid-PET individuals, a 1-unit DESH-pattern score increase correlated with 30%-greater odds of abnormal amyloid CSF after age, and sex adjustment. Mean rate over time of amyloid-PET accumulation in abnormal-CSF and/or normal-PET individuals approximated individuals with normal amyloid values. Adjusting for phosphorylated-tau, abnormal CSF-amyloid and/or normal amyloid-PET individuals had higher mean amyloid-PET accumulation rates than normal individuals. CSF dynamics disorders confound β-amyloid and phosphorylated-tau CSF-biomarker interpretation.
AB - Do MRI-based metrics of a CSF-dynamics disorder, disproportionately enlarged subarachnoid-space hydrocephalus (DESH), correlate with discordant amyloid biomarkers (low CSF β-amyloid 1–42, normal Aβ-PET scan)? Individuals ≥50 years from the Mayo Clinic Study of Aging, with MRI, 11C-Pittsburgh compound B (Aβ) PET scans, and CSF phosphorylated-tau protein and Aβ42, were categorized into 4 groups: normal and/or abnormal by CSF β-amyloid 1–42 and Aβ amyloid PET. Within groups, we noted MRI patterns of CSF-dynamics disorders and Aβ-PET accumulation-change rate. One-hundred participants (21%) in the abnormal-CSF and/or normal-PET group had highest DESH-pattern scores and lowest CSF-phosphorylated-tau levels. Among normal amyloid-PET individuals, a 1-unit DESH-pattern score increase correlated with 30%-greater odds of abnormal amyloid CSF after age, and sex adjustment. Mean rate over time of amyloid-PET accumulation in abnormal-CSF and/or normal-PET individuals approximated individuals with normal amyloid values. Adjusting for phosphorylated-tau, abnormal CSF-amyloid and/or normal amyloid-PET individuals had higher mean amyloid-PET accumulation rates than normal individuals. CSF dynamics disorders confound β-amyloid and phosphorylated-tau CSF-biomarker interpretation.
KW - Alzheimer's disease
KW - Amyloid PET accumulation
KW - Biomarkers
KW - Disproportionately enlarged subarachnoid-space hydrocephalus (DESH)
KW - Mayo Clinic Study of Aging (MCSA)
KW - Normal-pressure hydrocephalus
UR - https://www.scopus.com/pages/publications/85119956065
U2 - 10.1016/j.neurobiolaging.2021.10.017
DO - 10.1016/j.neurobiolaging.2021.10.017
M3 - Article
C2 - 34844077
SN - 0197-4580
VL - 110
SP - 27
EP - 36
JO - Neurobiology of aging
JF - Neurobiology of aging
ER -