By Biomarker Scientist Niccolo Fuin

Lots of biological motivation on AD progression and molecular biomarkers.

Most interesting session for me was: “Development Of New Models And Analysis Methods: Novel Imaging Analysis“ in which Pablo F. Damasceno (UCSF) shown a predictive model for Tau PET based on network diffusion that integrates structural connectivity with Tau measurements

Then Kay Jann (UCS Stevens Neuroimaging centre) shown how the fMRI complexity can be associated with Tau-PET and cognitive decline in Alzheimer’s disease offering a possibly simpler marker for monitoring and Patrick H Luckett (WashU in St. Luis) shown how deep learning models can reliably track the cognitive trajectories on multi-modal imaging data based on endpoints from amyloid PET, FDG and structural MRI in Autosomal Dominant Alzheimer Disease.

There were a few presentations on understanding, manipulating and prolonging cellular defence systems for therapeutic benefit. For example, Linda Greensmith (Department of Motor Neuroscience and Movement Disorders at the UCL Institute of Neurology) presented work on the use of the experimental drug Arimocolomol in ALS. This drug has been found to stimulate a normal cellular protein repair pathway by prolonging activation of heat shock proteins. SOD1 mouse models were found to have an 25% increase in lifespan and improvement in motion. The drug has also found to be well tolerated in healthy volunteers in a Phase I study.

Another interesting session was “Mechanism of white matter damage” where several speakers discussed molecular biomarkers for vascular and axonal damage. In particular, Joanna M Wardlaw (University of Edinburgh) discussed white matter hyperintensity (WMH) in the context of aging and AD. WHM can be identified on FLAIR scans and further characterised using DTI. During observational studies, WMH growth and shrinkage was observed. The speaker hypothesised that shrinkage was caused by resolved oedema in the area of interest. Understanding WMH is important as it relates to increased risk of dementia and stroke.

In the session of clinical heterogeneity in AD the presentation of Teresa Gomez-Isla (MGH/Harvard Medical School) was particularly interesting. She reported data from autopsy studies suggesting that not all individuals who harbour classic AD lesions in the brain (e.g.: plaques and tangles) will inevitably develop clinical symptoms of the disease during their life. These “resilient brains” are important to study as may hold important features for the design of novel neuroprotective therapies. The results reported suggests that is the tissue response of neural loss and synaptic derangement to plaques and tangles to determine the cognitive state of any individual. This raise the question: what do positive beta-amyloid and tau PET scans mean? It is not certain that people with plaques and tangles will develop symptoms of AD. The speaker highlights the need for better predictive biomarkers of cognitive decline beyond plaques and tangles to determine who and when will develop clinical symptoms of AD in their life.

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