Biofluid biomarkers increasingly play a number of different roles in drug discovery. Biomarkers of pathology identify subjects who already have the measurable effects of molecular pathology.
Recent advances in imaging, cognitive and other biomarkers now allow detection of individuals pre-clinically. Biomarkers of proximity take that assessment one step further by quantifying the imminence of clinical progression.
They may therefore offer the most relevant window of therapeutic opportunity during which the slowing of pathology would delay the onset of symptoms without including the wide heterogeneity of individuals who may be many years before clinical onset.
We better understand which changes indicate imminent clinical conversion in at-risk subjects and as such these ‘proximity’ markers allow targeting of individuals with most to gain from treatment with near certainty that they will otherwise become symptomatic within a definable time window.
Biomarkers will be important at all stages but are essential for testing therapies in individuals with pre-clinical disease. The ultimate aim of this combined approach is to find therapies that slow decline and delay clinical onset.
CSF Biomarkers and the Leonard Wolfson CSF Laboratory
CSF-based analyses are the most advanced of the biomarkers currently available in NDD. Aβ1-42 is decreased and tau and phosphorylated tau are increased in prodromal AD.
A number of novel CSF analytical techniques are in various stages of development, and show promise in improving diagnostic specificity in AD and as a means of identifying presymptomatic individuals.