GAP-43 as a biomarker for early diagnostics of Alzheimer’s disease

Abstract

Degree Project, Programme in Medicine. TITLE: GAP-43 as a biomarker for early diagnostics of Alzheimer’s disease Caroline Ström Supervisors: Magdalena Nutu, PhD & Henrik Zetterberg, MD, PhD

Abstract Background: For a long time research has focused on finding a cure for Alzheimer’s disease (AD) but progress in this regard has been slow. Today, when a person is diagnosed with AD, he or she is often in the dementia stage of the disease. In this stage of AD, the brain is already severely affected by the disease process and as much as 50% of the neurons in the hippocampus have already been lost. Therefore AD research is now focusing on finding tools for diagnosing AD at an early stage when neurons still can be saved. One possible biomarker for diagnosing AD is the protein GAP-43, playing a key role in the outgrowth and guidance of neural connections in both the central and peripheral nervous system. GAP-43 is abundantly expressed in the CNS and is also secreted into the cerebrospinal fluid (CSF) [1]. Here, we wanted to establish a method for measuring GAP-43 in CSF and serum using an immunochemical technique called Enzyme-Linked Immunosorbent Assay (ELISA). Methods: CSF samples from 42 individuals (21 with AD and 21 cognitively normal controls) were used in the study. We used a commercial ELISA kit for GAP-43 and we also worked on developing in house ELISA methods. Results: As expected, the AD and control groups were significantly different in regard to their levels of AD biomarkers in CSF. The commercial ELISA kit worked but could only measure GAP-43 in a subset of the samples due to suboptimal lower limit of detection. We have not yet succeeded in establishing definite in house ELISA methods, but preliminary data have been obtained. Conclusion: GAP-43 is present in CSF at concentrations that are too low to measure reliably using currently available commercial assays. Further method development is needed to obtain a good enough method to allow for characterization of GAP-43 levels in CSF.