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- W2897628560 abstract "Cerebrospinal fluid (CSF) biomarkers have become increasingly important in understanding the biology of Alzheimer's disease (AD). Under the ATN scheme of the new NIA-AA Research Framework, CSF biomarkers can be used to quantitate and stage each pathological process of AD. These include low CSF amyloid-beta(Aβ)-42 (or Aβ42/40 ratio) as a biomarker of β-amyloid plaques (“A”), elevated CSF phosphorylated tau (P-tau) as a biomarker of fibrillary tau (“T”), and elevated CSF total tau (T-tau) as a biomarker of neurodegeneration (“N”). While these CSF ATN definitions provide an updated frame work for staging AD biology, there are several challenges to the utility of these markers that need to be evaluated. We will discuss the challenges in using CSF biomarkers for operationalizing the NIA-AA AD Research Framework. Examples will be incorporated from the existing literature and data collected in the Mayo Clinic Study of Aging data. One challenge includes the relationship, and sometimes discordance, between CSF and neuroimaging measures of ATN. For example, in the Mayo Clinic Study on Aging (MCSA) the Spearman correlation between CSF Aβ42 and PiB-PET is -0.36 (p<0.001) among cognitively unimpaired participants. Further, it is currently unclear as to how to label individuals (A+ or A-) who have high CSF Aβ42 and high PiB-PET or low CSF Aβ42 and low PiB-PET. A second challenge is the determination of cut-points, which will likely differ depending on the utility of the marker. A third challenge is the use of CSF P-tau and T-tau as separate categories for “T” and “N”. CSF P-tau and T-tau are highly correlated (spearman rho = 0.98, p<0.001 in the MCSA). Therefore, it is unclear whether these markers are useful for measuring two separate biological processes. Despite these challenges, CSF provides an important opportunity to measure ATN and stage the NIA-AA AD Research Framework. Future directions for research will be highlighted and potential new CSF or blood-based markers that could be used for “T” or “N” will also be discussed." @default.
- W2897628560 created "2018-10-26" @default.
- W2897628560 creator A5090710393 @default.
- W2897628560 date "2018-07-01" @default.
- W2897628560 modified "2023-10-16" @default.
- W2897628560 title "FTS4‐01‐04: CHALLENGES IN USING CSF BIOMARKERS FOR OPERATIONALIZING THE NIA‐AA AD RESEARCH FRAMEWORK" @default.
- W2897628560 doi "https://doi.org/10.1016/j.jalz.2018.06.2904" @default.
- W2897628560 hasPublicationYear "2018" @default.
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