Presymptomatic plasma biomarkers in autosomal dominant Alzheimers disease: sequence and timing

The molecular pathology of Alzheimer’s disease develops many years before the onset of symptoms, and multiple plasma biomarkers of Alzheimer’s pathology have been identified. Understanding the timing of biomarker abnormality is important to guide trial design for the timing of interventions to prevent the onset of dementia.

Using an autosomal dominant Alzheimer’s disease cohort, we identify multiple plasma biomarkers that distinguish mutation carriers from non-carrier familial controls and characterise the timing of these changes relative to symptom onset. We demonstrate that biomarkers show change many years before symptom onset: markers of abnormal tau phosphorylation more than 20 years prior, followed by markers of reactive astrocytosis and synaptic dysfunction approximately 15 years prior and neurodegenerative markers within 10 years of symptoms.

Plasma biomarkers could...