Specialized Proteins Detected In Blood of Alzheimer's Disease Patients

In a select group of people who later developed dementia, the levels of the lysosomal proteins were abnormal while the people still had no problems with memory or thinking skills.

These specialized brain proteins that are involved in the removal of damaged nerve cell materials may be detected in the blood of people who were diagnosed with mild cognitive impairment or dementia due to Alzheimer's disease.

Scientists at the University of California, San Francisco (CA, USA) and their colleagues took blood samples from 20 people who later developed Alzheimer's disease up to 10 years before they were diagnosed and then after they were diagnosed. Blood also was taken once from 26 people with Alzheimer's disease and 16 people with frontotemporal dementia. In addition, blood samples were taken from 46 healthy people who did not have any problems with thinking or memory skills as a control group.

Cerebrospinal fluid (CSF) levels of total tau, phosphorylated PT181-tau, and Aβ 1-42 were quantified by Luminex xMAP technology (Luminex Corporation; Austin, TX, USA) using Innogenetics INNO-BIA Alzbio3 kits (Innogenetics; Ghent, Belgium). Exosome proteins were quantified by human-specific enzyme-linked immunosorbent assays (ELISAs) for total ubiquitin (FIVEphoton Biochemicals; San Diego, CA, USA).

The investigators searched for four proteins in blood exosomes that come from lysosomes. Lysosomes act as a sort of recycling and disposal center for cells. In each case, the level of protein was significantly different for the healthy controls than for those with dementia, both before and after symptoms developed. For three of the proteins, the people with dementia had significantly higher levels; for one of the proteins, the people with dementia had significantly lower levels. For example, for many proteins with an ubiquitin "tail," or unfolded portion, the healthy controls had average levels of 200 pg/mL, while the people with Alzheimer's disease had average levels of about 375 pg/mL.

Edward J. Goetzl, MD, a professor of medicine and lead author of the study said, “These proteins are in very tiny nerve cell-derived blood particles called exosomes. Abnormal levels of the proteins may be useful biomarkers that could help us study early treatments to limit or reverse the damage to brain cells and even prevent the development of the full-blown disease. The results also show us that there are major abnormalities in how these proteins function in brain cells, which could potentially provide a new target for treatments.” The study was published on June 10, 2015, in the journal Neurology.

Related Links:
University of California San Francisco 
Luminex Corporation 
Innogenetics