Biomarkers

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ResearchersAgainstAlzheimer's would like to thank Roche Diagnostics for their support of this project.
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Aβ1-42/ Aβ1-40 (CSF)

Method of Measurement (Pre-analytical Tools)
CSF
Biomarker Measured
Amyloid
Use
Diagnostic
Prognostic
Stage of Development
Clinical trials
Active vs Completed Trials
Completed
Aim/Results

The process of Aβ proteolytic cleavage generates the release of several Aβ isoforms, amongst which Aβ of 42 amino acids (Aβ1–42) has the highest propensity to aggregate into amyloid plaques. To increase concordance between amyloid markers, it has been suggested to apply shorter isoforms of Aβ (Aβ1–40 a) in order to calculate Aβ1–42/Aβ1–40 ratios. Aβ40 is the most abundant Aβ peptide isoform in the CSF. Compared with CSF Aβ42 levels alone, Aβ 42/40 ratio is suggested to account for the constitutive interindividual differences in total CSF Aβ peptide load between high- and low-amyloid-producing individuals.

What is Required from Patients

Invasive lumbar puncture, discomfort, recovery time in clinic to decrease risk of spinal fluid leakage

What is Required from the Health System

physician who can preform a lumbar puncture as well as a clinic designed for this testing, equipped lab (e.g., centrifuge), a way to measure the peptide (e.g., mass spectrometer, protein assay kit, ELISA, or western blot)

Sponsor

Multiple groups: e.g. see three papers referenced. Groups in Belgium, France,and Germany

  1. Dumurgier, J., Schraen, S., Gabelle, A., Vercruysse, O., Bombois, S., Laplanche, J. L., ... & Pasquier, F. (2015). Cerebrospinal fluid amyloid-β 42/40 ratio in clinical setting of memory centers: a multicentric study. Alzheimer's Research & Therapy, 7(1), 30. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4450486/

  2. Lewczuk, P., Lelental, N., Spitzer, P., Maler, J. M., & Kornhuber, J. (2015). Amyloid-β 42/40 Cerebrospinal fluid concentration ratio in the diagnostics of Alzheimer's disease: validation of two novel assays. Journal of Alzheimer's Disease, 43(1), 183-191. https://www.ncbi.nlm.nih.gov/pubmed/25079805

  3. Nakamura, A., Kaneko, N., Villemagne, V. L., Kato, T., Doecke, J., Doré, V., ... & Tomita, T. (2018). High performance plasma amyloid-β biomarkers for Alzheimer’s disease. Nature, 554(7691), 249. https://www.ncbi.nlm.nih.gov/pubmed/29420472

  4. Niemantsverdriet, E., Ottoy, J., Somers, C., De Roeck, E., Struyfs, H., Soetewey, F., ... & De Deyn, P. P. (2017). The Cerebrospinal Fluid Aβ 1–42/Aβ 1–40 Ratio Improves Concordance with Amyloid-PET for Diagnosing Alzheimer’s Disease in a Clinical Setting. Journal of Alzheimer's Disease, 60(2), 561-576. https://www.ncbi.nlm.nih.gov/pubmed/28869470