I know these proteins are generally measured using ELISA-based kits, but there's significant brand and batch variability associated with these tests.
Is anybody using mass spectrometry to look at these proteins or are there issues that makes this an impracticality?
Thanks
Hi, I agree with Marisol: Mass spectrometry will almost certainly add more variance rather than reducing it. Morever it is expensive and definitely not the method of choice for higher throughput. In view of the (relatively) well validated commercial solutions based on ELISA or Electrochemiluminescence for both analytes you mentioned, even with the option of multiplexing, I would not consider mass spec. The required sample volumes may also be an issue, especially in the case of CSF. The situation may be completely different, if you are intending to identify novel biomarkers: Here mass spec (and related approaches) may offer great opportunities.
There is a lot of work done in this field. A problem with immunoassays have been the great variability between assays and centers (see for example the papers from the Alzheimer's Association Quality Control Program, Mattsson N et al Alzheimer's & Dementia 2011 and Mattsson N et al Alzheimer's & Dementia 2013).
Mass spectrometry based assays for CSF AB42 have been introduced to overcome this variability. A candidate reference method for CSF Ab42 was recently published, based on LC-MS/MS, see Leinenbachet al. Clin Chem. 2014 Jul;60(7):987-94. ("Mass spectrometry-based candidate reference measurement procedure for quantification of amyloid-β in cerebrospinal fluid.") See also Korecka et al. J Alzheimers Dis. 2014;41(2):441-51"Qualification of a surrogate matrix-based absolute quantification method for amyloid-β₄₂ in human cerebrospinal fluid using 2D UPLC-tandem mass spectrometry." for a similar approach.
Mass spectrometry based methods for different Abeta isoforms have been used in several studies, using several different technologies, for an overview see Portelius et al, Curr Pharm Des. 2011;17(25):2594-602. "Novel aβ isoforms in Alzheimer's disease - their role in diagnosis and treatment."
Mass spectrometry based methods are also being developed for CSF tau, although this has been more challenging.
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