Blood Progranulin May Not Be Suitable Alzheimer’s Marker After All, Researchers Find

Recent hopeful statements that blood levels of progranulin might be a biomarker for Alzheimer’s disease and other forms of dementia came to an abrupt stop when a recent study demonstrated that there is no link between the blood and cerebrospinal fluid levels of the substance, disrupting the idea of a progranulin blood test for dementia. The study, however, advances our understanding of disease processes in dementia, and prevents future studies from following the wrong track.

While mutations in the progranulin gene, GRN, have been linked to hereditary forms of dementia, researchers agree that the factor also plays an important part in sporadic dementia cases where no mutations are present. Based on these findings, scientists had proposed that low levels of progranulin could serve as a biomarker for Alzheimer’s disease and other neurodegenerative conditions.

The substance, which is a growth factor with anti-inflammatory and neurotrophic properties, has also been suggested as a potential treatment for dementia. The new study, led by Carlo Wilke and Matthis Synofzik of the Hertie-Institute for Clinical Brain Research & German Center for Neurodegenerative Diseases (DZNE) and the University of Tübingen in Germany, shows a more complicated picture of progranulin regulation than scientists had anticipated.

The team measured the molecule in blood and cerebrospinal fluid — the liquid surrounding the brain and spinal cord — in patients with Alzheimer’s, frontotemporal dementia and amyotrophic lateral sclerosis (ALS), and found that the blood levels did not mirror the brain concentration of progranulin.

The study, published in the journal Current Alzheimer Research under the title “Serum Levels of Progranulin Do Not Reflect Cerebrospinal Fluid Levels in Neurodegenerative Disease,” suggests that different mechanisms control levels of the factor in the brain and blood.

The results are likely disappointing for researchers in both academic and industrial settings who have focused on a presumed link between blood progranulin and dementia. The study shows that analyzing the substance in a blood sample will tell us little about neurodegenerative processes taking place in the brain.

These key findings may have saved years of research and millions of dollars in studies focusing on peripheral levels.