Our Webinar on 17 June 2013 covered the latest research and future directions on blood-based biomarkers discussed at a recent Alzheimer’s Drug Discovery Foundation/Alzheimer’s Association conference. Sid O’Bryant, Texas Tech University, Lubbock; Samantha Burnham, Commonwealth Scientific and Industrial Research Organisation, Perth, Western Australia; Simon Lovestone, King’s College, London, U.K.; Eugenia Trushina, Mayo Clinic Rochester, Minnesota; and Henrik Zetterberg, University of Gothenburg, Sweden, presented. Guest moderator Howard Fillit of ADDF, New York City, led a subsequent discussion and took audience questions.
We thank Alzheimer's Research & Therapy for free access to this paper:
Zetterberg H, Wilson D, Andreasson U, Minthon L, Blennow K, Randall J, Hansson O. Plasma tau levels in Alzheimer's disease. Alzheimer's Res Ther. 2013 Mar 28;5(2):9. Read article.
Burnham SC, Fau NG, Wilson W, Laws SM, Ames D, Bedo J, Bush AI, Doecke JD, Ellis KA, Head R, Jones G, Kiiveri H, Martins RN, Rembach A, Rowe CC, Salvado O, Macaulay SL, Masters CL, Villemagne VL, Alzheimer’s Disease Neuroimaging Initiative. Australian Imaging, Biomarkers and Lifestyle Study Research Group. A blood-based predictor for neocortical Aβ burden in Alzheimer’s disease: results from the AIBL study. Molecular Psychiatry (2013), 1–8. Read article.
Listen to the Webinar.
Howard Fillit's Presentation
Sid O’Bryant's Presentation
Simon Lovestone's Presentation
Samantha Burnham's Presentation
Henrik Zetterberg's Presentation
Eugenia Trushina's Presentation
By Diana Shineman (ADDF) and Gabrielle Strobel
If researchers could measure the biochemical changes associated with Alzheimer’s disease many years before symptoms develop, they could better devise treatments to arrest the disease process before a person loses brain function. Researchers need such markers for early diagnosis to stratify individuals for clinical trials and to monitor response to investigational therapies. The most established biomarkers today come from brain imaging or CSF protein assays. Many clinicians would prefer markers based on a simple blood draw, but research in this area has thus far generated no widely accepted candidates. On 12 April 2013, 30 researchers gathered in New York City to discuss the current state of research on blood-based biomarkers in Alzheimer’s disease and to showcase a renewed push to achieve this goal. The Alzheimer’s Drug Discovery Foundation and the Alzheimer’s Association jointly hosted the meeting.
To date, most AD plasma work has been to measure levels of β amyloid, and this has been used in some clinical trials to monitor treatment response. However, scientists disagree about how closely blood Aβ levels reflect Alzheimer’s disease in the brain (see review by Toledo et al., 2013). Attempts to correlate other plasma markers with disease progression have not yet panned out. Prior efforts to measure tau have been stymied by insensitive assays, though Zetterberg and colleagues reported this past March that with a new assay they can detect as little as 0.02 pg/ml of tau in plasma. Others, including Burnham, have identified plasma marker panels, but so far these panels lack the sensitivity and specificity required for diagnostic or prognostic use. In April, Burnham reported results from the longitudinal AIBL study, which draws repeated blood samples from a large sample of elderly people in Australia (see Burnham et al., 2013).
As outlined in a recent review (see Galasko and Golde, 2013), the goal of finding plasma, serum, or blood biomarkers for a central nervous system disease confronts conceptual and practical challenges.
There are other hurdles to cross as well. Currently available plasma assays suffer from significant variability. On that issue, ongoing efforts to standardize and optimize cerebrospinal fluid assays provide lessons that can be applied to blood-based biomarkers and potentially enable this field to harmonize protocols earlier on.
While no blood-based tests are ready for commercial or clinical diagnostic use, there may be a benefit to using them in combination with other biomarkers to gather additional information from trials. In addition to disease-specific markers of pathology, such as Aβ, increasingly active avenues of exploration have opened up around new biomarkers of neuronal function and neurodegeneration, including inflammatory markers, gene expression changes, proteomics, and metabolomics. Such markers hold out the promise of an eventual blood test for Alzheimer’s, although more discovery and standardization are needed.
Burnham SC, Fau NG, Wilson W, Laws SM, Ames D, Bedo J, Bush AI, Doecke JD, Ellis KA, Head R, Jones G, Kiiveri H, Martins RN, Rembach A, Rowe CC, Salvado O, Macaulay SL, Masters CL, Villemagne VL, Alzheimer’s Disease Neuroimaging Initiative. Australian Imaging, Biomarkers and Lifestyle Study Research Group. A blood-based predictor for neocortical Aβ burden in Alzheimer’s disease: results from the AIBL study. Molecular Psychiatry (2013), 1–8.
- Toledo JB, Shaw LM, Trojanowski JQ. Plasma amyloid beta measurements - a desired but elusive Alzheimer's disease biomarker. Alzheimers Res Ther. 2013 Mar 8;5(2):8. PubMed.
- Burnham SC, Faux NG, Wilson W, Laws SM, Ames D, Bedo J, Bush AI, Doecke JD, Ellis KA, Head R, Jones G, Kiiveri H, Martins RN, Rembach A, Rowe CC, Salvado O, Macaulay SL, Masters CL, Villemagne VL, . A blood-based predictor for neocortical Aβ burden in Alzheimer's disease: results from the AIBL study. Mol Psychiatry. 2013 Apr 30; PubMed.
- Galasko D, Golde TE. Biomarkers for Alzheimer's disease in plasma, serum and blood - conceptual and practical problems. Alzheimers Res Ther. 2013 Mar 7;5(2):10. PubMed.
- Kordower JH, Emborg ME, Bloch J, Ma SY, Chu Y, Leventhal L, McBride J, Chen EY, Palfi S, Roitberg BZ, Brown WD, Holden JE, Pyzalski R, Taylor MD, Carvey P, Ling Z, Trono D, Hantraye P, Déglon N, Aebischer P. Neurodegeneration prevented by lentiviral vector delivery of GDNF in primate models of Parkinson's disease. Science. 2000 Oct 27;290(5492):767-73. PubMed.