O'Bryant SE, Xiao G, Barber R, Reisch J, Doody R, Fairchild T, Adams P, Waring S, Diaz-Arrastia R, .
A serum protein-based algorithm for the detection of Alzheimer disease.
Arch Neurol. 2010 Sep;67(9):1077-81.
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The study presented by the Texas Alzheimer’s Research Consortium (TARC) is one in a series of recent publications supporting the concept that changes in the levels of blood-based proteins may be associated with Alzheimer disease and related conditions. While there is little agreement yet about which proteins may be the best predictors or classifiers of AD, proteins such as TNFα, MCP1, ICAM1, and others seem to be featured in several published “signatures.” A more critical interpretation of these results is that the selected proteins are generic “inflammatory” markers, which may simply be indicative of some level of immune activation not specific to AD patients. Only biological studies done in cell culture or animal models can start to determine their potential pathophysiological relevance.
The TARC study used serum instead of plasma to derive a signature, and it can be debated whether this is an advantage or not. The collection of both plasma and serum pose significant challenges in the clinic, and protocols are difficult to standardize. The size of the needle used in phlebotomy, the speed of blood collection, or the storage before centrifugation are just a few of the variables that can affect the stability of proteins or lead to degranulation of platelets and the release of many cytokines and growth factors. The TARC study may also suffer from age bias, a problem that may also have affected the results from our own study published in 2007 (Ray et al., 2007). Unpublished data from our lab show that many cytokines and related factors change significantly with age.
A biomarker consortium funded by the Foundation of the NIH, Rules-Based Medicine, and Satoris Inc. has recently measured close to 200 secreted signaling proteins and related factors in over 1,000 plasma samples from the ADNI study, and these results will hopefully soon become available to the public. Ideally, raw data from the TARC study, as well as other recently published studies, will be released to the public as well to allow for large meta-analysis of all data. Geneticists have set an example of how to pool SNP data on AD risk factors and come up with an annotated hit list of most relevant factors (see AlzGene resource).
Ray S, Britschgi M, Herbert C, Takeda-Uchimura Y, Boxer A, Blennow K, Friedman LF, Galasko DR, Jutel M, Karydas A, Kaye JA, Leszek J, Miller BL, Minthon L, Quinn JF, Rabinovici GD, Robinson WH, Sabbagh MN, So YT, Sparks DL, Tabaton M, Tinklenberg J, Yesavage JA, Tibshirani R, Wyss-Coray T.
Classification and prediction of clinical Alzheimer's diagnosis based on plasma signaling proteins.
Nat Med. 2007 Nov;13(11):1359-62.
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