Kaj Blennow

Symposium Description

Neurodegenerative diseases are complex issue that affects millions of people and their families around the worlds. Estimations are more worrying, since number of cases will only increase in the future. Most common neurodegenerative diseases are Alzheimer’s Disease (AD) and Parkinson’s Disease (PD). Symptoms for those develop over years, and early diagnosis is critical to have a chance to improve people lives. This symposium will focus on current biomarkers of neurodegenerative diseases. The best indicators would be markers that are detectable before changes in magnetic resonance imaging (MRI) or positron emission tomography (PET) are observed. Ideally, those biomarkers could be factors engaged in development of pathological changes and would inform us about disease progression. Invited speaker is prof. Kaj Blennow, who achieved medical degree in 1984 at Lund University, and has specialist competence in General Psychiatry and Clinical Chemistry. He is professor in Clinical Neurochemistry at University of Gothenburg and has over 1200 original publications. His current research interest focuses on fluid biomarkers in neurodegenerative diseases, mostly AD. Pathologic AD changes in living people can be done using fluid biomarkers or neuroimaging. Currently, the core fluid biomarkers for an “AD profile” are CSF amyloid β (Aβ) 42 (or Aβ42/Aβ40 ratio), which reflects amyloid-β plaque pathology; phosphorylated-tau (p-tau), which is an indicator of fibrillar tau and/or tau phosphorylation; and total-tau (t-tau) or neurofilament light (NfL), a neuronal injury or neurodegeneration markers. Diagnosis and prediction of AD can be further improved by novel blood p-tau biomarkers, which similarly to CSF p-tau are more specific than plasma Aβ42/40, total tau or NfL. Currently under exhausting research in his lab are p- Tau181; p-Tau217 and p-Tau231 species, which, regarding to CSF, plasma and brain tissue are very useful as early biomarkers in AD continuum.  

Talk: "CSF and plasma biomarkers for Alzheimer’s disease – update on performance and applications in the clinic"

Cerebrospinal fluid (CSF) biomarkers reflecting the core AD pathologies amyloid deposition (A), tau pathology (T), neurodegeneration (N) have been developed and show very high performance for diagnosis. These tests are also available on fully automated lab analyzers, with superior precision. Newly developed blood biomarkers for AD show promise for use as screening tools and therapy monitoring, which will be of great importance when the new amyloid immunotherapies will be available in the clinic.
The plasma Ab42/40 ratio, measured using either immunoassays or immunoprecipitation - mass spectrometry (IP-MS) methods show high concordance (AUCs of 80-90%) with brain amyloidosis evaluated by PET. However, the effect size (fold change) in PET positive cases for the Ab42/40 ratio is low, when measured in plasma, with only around 10% decrease and a major overlap.
Very promising data have been reported for several phosphorylated tau species (P-tau181, P-tau217, and P-tau231) in blood, showing a specific increase in AD and high concordance with tau PET. In addition, plasma P-tau is increased in cognitively unimpaired elderly who have positive amyloid, but negative tau, PET scans. Recent studies show high correlations between these P-tau species in both CSF and plasma, suggesting that differences are minor.
Neurofilament light (NFL) levels are increased in both CSF and blood in AD, but NFL is a general neurodegeneration biomarker showing high levels in many other neurodegenerative disorders. AD. High plasma GFAP is also found in cases with PET evidence of brain amyloidosis and shows promise as a biomarker for glial activation and neuroinflammation.
To implement the blood biomarkers in clinical routine diagnostics, data on the robustness of these biomarkers is needed. For a robust biomarker, the combined biological, pre-analytical, and analytical variability is markedly lower than the fold change (percent difference between patients and controls), also with repeated measurements. For this reason, blood biomarkers may better fit for risk prediction, in algorithms together with APOE and age, than as diagnostic tools. Even so, blood biomarkers will be very useful in the clinical setting.