Cerebrospinal fluid dynamics and discordant amyloid biomarkers

Jonathan Graff-Radford, David T. Jones, Heather J. Wiste, Petrice M. Cogswell, Stephen D. Weigand, Val Lowe, Benjamin D. Elder, Prashanthi Vemuri, Argonde Van Harten, Michelle M. Mielke, David S. Knopman, Neill R. Graff-Radford, Ronald C. Petersen, Clifford R. Jack, Jeffrey L. Gunter

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)27-36
Number of pages10
JournalNeurobiology of aging
StatePublished - Feb 2022


  • Alzheimer's disease
  • Amyloid PET accumulation
  • Biomarkers
  • Disproportionately enlarged subarachnoid-space hydrocephalus (DESH)
  • Mayo Clinic Study of Aging (MCSA)
  • Normal-pressure hydrocephalus

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology


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