(199 Total References)
Kaj Blennow, MD, PhD
Kaj Blennow, MD, PhD is a professor at Sahlgrenska University Hospital in Goteborg, Sweden.
conducts research on the mechanisms behind neurological disorders and over the past twenty (20) years, he
has developed biochemical tests for Alzheimer's disease.
He is a world-renowned researcher and clinician in both concussion and Alzheimer's disease.
Kaj Blennow of the ...
Kaj Blennow of the University of Gothenburg, Sweden, updated the group on the status of fluid markers in FTD.
If so, further mass spectrometry studies may identify fragments that could serve as the basis of FTD-specific tau assays, Blennow
said (Portelius et al., 2008; Meredith et al., 2013).
A week after the FTSG meeting, on April 7, Blennow
received Sweden's 2016 Söderberg Prize in Medicine.
The new darling in the AD biomarkers field-neurogranin-also appears to be a non-starter in FTD
Neurogranin has long been known to be a component of dendritic spines, and new antibodies to it have led to tests that are rapidly gathering evidence supporting neurogranin as a CSF marker for synaptic degeneration in Alzheimer's.
Alas, the few studies that have thus far compared neurogranin across a range of dementing disorders suggest its signature increase may be specific to AD.
This means the current AD fluid markers are useful indirectly, because they help exclude an FTD diagnosis, Blennow
Could a blood test measure it accurately to spot FTD? [Courtesy of Kaj Blennow
, U. Gothenburg.]
Could a blood test detect NFL?
It's a tall order.
Compared to NFL's concentration in the CSF (500 pg/ml), its concentration in plasma is but 10 pg/ml.
This amounts to 3 percent of a sugar cube's worth of NFL dissolved in an Olympic-size swimming pool that also contains 40 tons of other proteins, Blennow
Abundant proteins such as CSF albumin would weigh in at 350 kg in the same pool.
But according to Blennow
, a single molecule array (aka Simoa) assay can do it.
The assay uses capture and biotin-tagged detection antibodies, as do ELISAs, but its bead-based technology and digital readout give it greater sensitivity.
It measures NFL in serum down to a limit of 0.6 pg/ml, as compared to 78 pg/ml for ELISA and 16 pg/ml for Mesoscale.
"You need these kinds of ultrasensitive technique to measure NFL in blood," Blennow
A single molecule array assay is more sensitive than ELISA, enabling scientists to detect neurofilament light chain in serum in the vanishingly low concentrations at which it occurs in human blood (blue box). [Courtesy of Kaj Blennow.]
Further data showed that NFL in blood correlates tightly with NFL in CSF; in other words, that serum NFL reflects brain pathology.
With this reassurance, Blennow
and collaborators at University College London
tried the new test on blood samples of various FTD subgroups.
Initial analyses of GENFI and other samples are beginning to show elevated serum NFL in all FTD subgroups, particularly in FTD-ALS and in progranulin mutation carriers, Blennow
"Plasma NFL is a sensitive but unspecific progression marker for neurodegeneration," Blennow
As a candidate progression marker, could it flag a treatment effect in trials?
There is no FTD data yet, but in multiple sclerosis, the answer is yes, at least according to a study in which blood NFL levels returned to normal in patients who responded to natalizumab antibody treatment (Gunnarsson et al., 2011).
If blood NFL holds up in further testing, it may obviate the need for spinal taps in FTD
What about blood proteomics and metabolomics?
Most studies on multiple-ligand assays have started with up to 1,200 molecules and ended with panels of 18 or less that reportedly discriminate between groups.
Typically, the changes in individual ligands are minute but collectively, their change can be significant in a statistical model.
The small number of patients in these studies raises a concern of data over fitting, Blennow
Biomarker studies need to move beyond validating a panel by dividing the original cohort into a training and a validation set and adjusting the panel to optimize its discriminatory power.
The way toward a robust assay is to take the panel to a totally different sample of people and try to validate the original finding.
"Fix your panel and test it in a new cohort.
If you can do that three, four times, then you have something," Blennow
What about cytokines?
noted that despite the growing interest in neuroinflammation in neurodegenerative disease research, general inflammation markers are difficult to measure.
Cytokines are present at low levels of 1 to 2 pg/ml and tend to hover at the bottom of their assays' calibration curves.
recommended investigators run their samples alongside samples from multiple sclerosis or a chronic infectious disease such as Lyme
to gain a sense of how cytokine changes in FTD
compared to those in known neuroinflammatory conditions.
"You typically see a slight change in AD or FTD
compared to an enormous difference in MS," Blennow
Scientific Advisory Board | Alzheon
Kaj Blennow, MD, PhD
Professor of Clinical Neurochemistry, University of Gothenburg, Sweden
Head of Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Gothenburg, Sweden
Alzheimer's Association Partnerships | Biomarker Projects
To address these issues, Kaj Blennow, M.D., Professor of Clinical Neurochemistry at the University of Gothenburg (Sweden), drafted a survey to be completed by European AD investigators engaged in CSF assays for AD research or practice.
Dr. Blennow invited representatives from Washington University, St Louis, to develop the survey further and introduce it to the Alzheimer's Disease Centers (ADCs).
Kaj Blennow, University ...
Kaj Blennow, University of Gothenburg, Sweden