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For the first time, scientists of the university of Georgetown (US), found biomarkers for Alzheimer’s Disease (AD) in blood samples, which were present before any visible symptoms of AD were visible. Last weekend, they published their results in Nature Medicine. These biomarkers could detect AD two to three years before any detectable memory or function loss. MedZine spoke about this development to prof. dr. Philip Scheltens, who is a professor in cognitive neurology and director of the Alzheimer Center at the VU medical center in Amsterdam, and dr. ir. Charlotte Teunissen, who is head of the neurochemistry laboratory at the VU medical center in Amsterdam and an expert on AD biomarkers.

Phospholipid biomarkers
Ten phospholipid metabolites were found of which the blood values in (future) AD patients were decreased. The research consisted of a five-year cohort study where blood values of 107 people over the age of 70 years were compared by mass-spectrometry. Of this group, 35 people showed signs of AD at the start of the research and 18 developed AD symptoms during study. Scheltens: “It’s the first time applicable biomarkers for AD are found in the blood. Still, the groups are quite small.” Current methods are invasive and/or expensive. Teunissen adds that this method is still very expensive but a lot less invasive than earlier used methods. “There is a long way to go before this method could detect AD on individual patients. We should investigate whether this method could be translated to a technology applicable in larger cohorts. This would make it possible to repeat the research in such a way that all ins and outs could be explored”, says Teunissen.

The relation to the disease
Currently, it is unknown what the relation of these particular lipids to the underlying mechanisms of AD is. Scheltens: “It’s very interesting that it’s phospholipids that were found. We know that these form an important element in synapses of neurons.” Federoff, lead investigator of this study, thinks these decreased levels directly reflect the breakdown of neuronal cell membranes, as is the case in AD. Teunissen: “Hopefully, we can connect these phospholipids to a specific mechanism underlying AD. At the moment, this is impossible, because these phospholipids are linked to multiple aspects of the disease.” According to Scheltens this study proves the importance of these substances  in an early stage of AD.

Dementia research at the VUmc
At the Alzheimer Center and the Neuroscience Campus Amsterdam, both at the VU, neurodegenerative diseases are a main research topic. Scheltens and Teunissen are starting up a study that focuses on finding metabolites as biomarkers for dementia. According to Teunissen it’s not very uncommon that much discussed publications like these turn out to be irreproducible. Teunissen adds: “I’ll certainly try to see whether these results are reproducible. We can apply this in our current research and we’ll certainly do.”

Clinical relevance
Since the clinical relevance of these biomarkers could be high, further research is needed. Early tracing of AD could advance research on target molecules for medication and possibly, in the long term, lead to early screening on AD among the population. AD therapies can only combat symptoms and slow down the course of the disease, but a curative treatment is unavailable at the moment. Worldwide there are 35 million dementia patients and the prospect is that this will rise to 115 million in 2050. Dementia is a very aggravating disease for patients and their family and friends and forms a major expense in healthcare. Therefore, developments that can lead to better diagnosis and treatment are of interest. 

Source: Mapstone et al. Nature Medicine (2014).