Version

This documentation pertains to Freeze 2023_May of the C2N Precivity - St. Louis dataset.

Origin

These plasma assays come from C2N Diagnostics. 

Sample selection

Samples were included from observations at which at least one aliquot of EDTA plasma was available for participants who had also had at least one amyloid PET scan or at least one lumbar puncture. Only one observation was included per participant.
This dataset includes 330 observations on 330 participants (57 ADRC; 224 female; 25 URG; 28 MCI and 5 Dementia at first visit; 28 MCI and 5 Dementia at last visit; mean first and last ages of 67.9 and 67.9, respectively). Per data sharing agreements with the Oneida nation, data from Native American participants are not included in this dataset.


Analytes:

• Amyloid beta 40 [LC-MS/MS]
• Amyloid beta 42 [LC-MS/MS]
• Non-phosphorylated tau 181 concentration [nanoLC-MS/MS]
• Non-phosphorylated tau 217 concentration [nanoLC-MS/MS]
• Phosphorylated tau 181 concentration [nanoLC-MS/MS]
• Phosphorylated tau 217 concentration [nanoLC-MS/MS]

Derived Variables:

• Amyloid beta 42/40 ratio
• Amyloid Probability Score (PrecivityAD)
• Phosphorylated tau 181 ratio
• Phosphorylated tau 217 ratio

Detection Limits:

• Ab40: functional LLOQ = 11-26400 pg/mL
• Ab42: clinically reportable range = 2-3920 pg/mL
• pTau181: not reported
• pTau231: not reported

Methods

The PrecivityAD score is a proprietary score combining information about amyloid and APOE into a number ranging from 0-100. Higher scores indicate a higher probability of a positive signal on amyloid PET. The package insert for clinicians suggests the following ranges: Low=0-35; Intermediate=36-57; High=58-100. Clinical recommendations are that Low scores are inconsistent with an Alzheimer's disease diagnosis, and therefore other causes for any cognitive symptoms should be investigated; that High scores are consistent with a high likelihood of amyloid plaques, but that amyloid alone is insufficient for an Alzheimer's disease diagnosis, and clinical presentation must also be considered; and Intermediate scores require further diagnostic evaluation to assess the underlying cause of any cognitive symptoms. See documentation here: https://precivityad.com/healthcare-providers-faqs

More information on the amyloid assays and the Precivity score can be found here:

Kirmess KM, Meyer MR, Holubasch MS, et al. The PrecivityAD™ test: Accurate and reliable LC-MS/MS assays for quantifying plasma amyloid beta 40 and 42 and apolipoprotein E proteotype for the assessment of brain amyloidosis. Clin Chim Acta. 2021;519:267-275. https://doi.org/doi:10.1016/j.cca.2021.05.011 

For the pTau assays, the recommendation is to use a measure of phosphorylation occupancy at the relevant threonine location. As this is a ratio, it is unitless and has no lower limit of detection. For more details, see:

Barthélemy NR, Horie K, Sato C, Bateman RJ. Blood plasma phosphorylated-tau isoforms track CNS change in Alzheimer's disease. J Exp Med. 2020;217(11):e20200861. https://doi.org/doi:10.1084/jem.20200861

Data Dictionary

Funding / Acknowledgments

Papers including data obtained from these assays should acknowledge NIH R01 AG027161 (the Wisconsin Registry for Alzheimer's Prevention) and/or NIH P30 AG062715 (the Wisconsin Alzheimer's Disease Research Center).