Emerging plasma biomarkers of Alzheimer’s disease might be non-invasive tools to trace early Alzheimer’s disease-related abnormalities, such as the accumulation of amyloid-beta peptides, neurofibrillary tau tangles, glial activation, and neurodegeneration. However, it is unclear which peripheral measurements can adequately detect pathological processes in the CNS and whether plasma biomarkers are equally applicable in clinical and preclinical phases.
In a new study, scientists at Karolinska Institutet explored the timing and performance of plasma biomarkers in mutation carriers compared to non-carriers in autosomal dominant Alzheimer’s disease. The study shows that a protein called GFAP is a possible biomarker for the very early stages of the disease.
The scientists examined 164 blood plasma samples from 42 relatives without inherited pathogenic risk and 33 mutation carriers for their investigation. The information was gathered between 1994 and 2018. Their results reveal clear changes in several blood protein concentrations in the mutation carriers.
The last author Caroline Graff, professor at the Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, said, “The first change we observed was an increase in GFAP (glial fibrillary acidic protein) approximately ten years before the first disease symptoms. This was followed by increased concentrations of P-tau181 and, later, NFL (neurofilament light protein), which we already know is directly associated with the extent of neuronal damage in the Alzheimer’s brain. This finding about GFAP improves the chances of early diagnosis.”
Charlotte Johansson, a doctoral student at the Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, said, “Our results suggest that GFAP, a presumed biomarker for activated immune cells in the brain, reflects changes in the brain due to Alzheimer’s disease that occur before the accumulation of tau protein and measurable neuronal damage. In the future, it could be used as a non-invasive biomarker for the early activation of immune cells such as astrocytes in the central nervous system, which can be valuable to the development of new drugs and the diagnostics of cognitive diseases.”
Journal Reference:
- Charlotte Johansson, Steinunn Thordardottir, et al. Plasma biomarker profiles in autosomal dominant Alzheimer’s disease. Brain. DOI: 10.1093/brain/awac399