Cerebrospinal fluid dynamics and discordant amyloid biomarkers

Abstract

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.

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