Biomarkers

Area of Science:

• Neurology
• Biomarker Discovery
• Neuroimaging

Background:

• Coexisting Alzheimer's disease (AD) and cerebrospinal fluid (CSF) dynamic disorders, such as normal-pressure hydrocephalus (NPH), can alter CSF Aβ42 levels, complicating AD biomarker interpretation.
• The influence of CSF dynamics on plasma-based AD biomarkers remains largely unexplored.
• This study investigated the association between MRI-detected disproportionately enlarged subarachnoid space hydrocephalus (DESH) and mass spectrometry-based plasma AD biomarkers.

Purpose of the Study:

• To determine if plasma Alzheimer's disease (AD) biomarkers, measured via mass spectrometry, are associated with disproportionately enlarged subarachnoid space hydrocephalus (DESH) identified on MRI.
• To assess the impact of CSF dynamics on the reliability of plasma AD biomarkers.

Main Methods:

• Utilized data from 509 participants in the Mayo Clinic Study of Aging, including MRI, Aβ PET scans, and plasma biomarkers (phosphorylated-tau protein 217, Aβ40, Aβ42).
• Performed age-adjusted logistic regression to evaluate the association between abnormal plasma biomarker levels (p-Tau 217, %p-tau217, Aβ42, Aβ42/40 ratio) and the presence of DESH.
• DESH classification was based on a validated automated MRI algorithm.

Main Results:

• Thirty-two participants were identified as DESH-positive.
• An abnormal plasma Aβ42 level was significantly associated with DESH (OR, 2.56; p=0.018).
• No significant association was found between DESH and abnormal plasma p-tau217 or %p-tau217. Subgroup analysis revealed that abnormal Aβ42 combined with positive amyloid PET was associated with DESH.

Conclusions:

• Plasma Aβ42 levels are influenced by CSF dynamics, specifically DESH, consistent with prior CSF studies.
• Plasma p-tau217 demonstrates robustness against DESH, suggesting its suitability as a biomarker in individuals with abnormal CSF dynamics.
• Further validation in populations with more severe CSF dynamic disorders is recommended for p-tau217.