Breteler suggested that biomarker data can be used to define more homogeneous groups within the very heterogeneous population of AD patients. This could help facilitate more specific, targeted clinical trials and help to identify effects in specific subgroups.

Another benefit of having validated biomarkers of prodromal AD will be the ability to conduct epidemiological studies of Alzheimer’s disease versus Alzheimer’s dementia. Breteler noted that measurement of cholesterol has been very successfully used in studies because it is a relatively inexpensive test requiring only a blood sample. To better understand prodromal AD in the population at large and develop preventive interventions, Breteler suggested that there is a need for easier, cheaper, standardized, more accessible biomarker tests for the early stages of AD.

A participant from industry discussed the development and recruitment of the first prodromal AD clinical trial based on the International Working Group guidelines, and the specific challenges of operationalizing the guidelines. He opined that even with the methodology standardization issues, there is still overwhelming evidence that Alzheimer’s pathology reflected through CSF biomarkers predicts progression to Alzheimer’s dementia. His view is that these studies can be done now, and will improve incrementally as better, standardized assays are available. The available assays for these biomarkers can be carefully used, in parallel to the other mechanisms, to identify those at risk and enrich the study population of a trial.

Although the new guidelines geared toward defining preclinical AD are clearly defined as being for research purposes only, some participants acknowledged that there will be great interest in applying these guidelines in the clinic as well. Specifically, biomarkers may be a useful diagnostic tool when incorporated into the examination by skilled physicians. Individuals in their 50s and 60s are eager to know their risk, often because a parent or grandparent has AD.

Overall, the panel agreed that the new guidelines are not an end point, and it will be important to continue to incorporate new insights and challenge the existing thinking. Moving forward, revisiting the guidelines on a regular basis as new data becomes available will be important, as well as maintaining a multidisciplinary global dialogue.



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