Friday, February 9, 2024

Genomeweb Article Features Diagnostic Alzheimer Blood Tests

 Header:  See a detailed review of rapidly emerging Alzheimer blood tess, especially pTau217.


I did an MD-PhD with the intention of working in Alzheimer's research, and neuro disease was my focus from 1988 to 2001.   Even in the 90's, there were regularly promises of a new Alzheimer blood test, which never panned out.

So I was excited to see a feature article in 360Dx by Adam Bonislawski about the rapid publications and advances in Alzheimer blood tests.   Both plasma ABeta 42/40 ratio and Tau epitopes are promising.  The article focuses on large new clinical reports that highligh phopho-Tau 217.   

Bonislawsky writes, 

  • "Plasma phosphorylated-tau 217 (p-tau 217) has emerged as a highly promising marker of the brain amyloid pathology characteristic of Alzheimer's and one that could lessen demand for plasma amyloid-beta 42/40 (Aβ42/Aβ40), the first blood-based marker for the disease to come to market."
New papers include Yu et al., Plasma p-tau181 and p-tau217 in discriminating PART, AD and other key neuropathologies in older adults.   And Ashton et al., Diagnostic ccuracy of a Plasma Phosphorylated Tau 217 Immunoassay for Alzheimer Disease pathology.

Twists and Ins and Outs

I think a couple factors have made the space hard to summarize.  First, as these titles indicate, it's not just "tau" or even "phospho-tau" but specific epitopes may behave differently.   

Then, there is not one single "phospho tau 217" assay.   Most assays require two antibodies, a  capture and a detection, and those will vary among platforms.   

Then, there are different detection platforms (e.g. the Quanterix Simoa technology is a differentiated technology).  

Finally, even when those platform variables are settled, there are many ins and outs to defining sensitivity and specificity.  Is there a gold standard besides autopsy?   What do decimal-point clinical statistics mean, if the clinical gold standard is wrong 20% or 30% of the time?    

And what populations does a statistic pertain to?   Health controls versus advanced patients?  That probably gives the best statistics but it compares extremes that don't match a clinical question (which is in the  early symptoms patient.)  So if someone pronounces  a factoid like, "Plasma tau is 81.5% specific" you really don't know what that means without more facts.