Major risk factors for Alzheimer's disease: age and genetics

摘要

Blood-based biomarkers are becoming increasingly important for the diagnosis and prognosis of Alzheimer's disease. In the past, the only validated biomarkers for Alzheimer's disease were amyloid PET and CSF amyloid β. Now we have the real prospect that blood biomarkers can be added to the list. There is still much work to be done to confirm their validity, but the signs so far are very promising. In The Lancet Neurology, Yakeel Quiroz and colleagues convincingly show the correlations between plasma neurofilament light chain (NfL) concentrations and age and genetic status in a very large cohort of 1070 presenilin 1 (P5EN1) E280A (Glu280Ala) mutation carriers and 1074 age-matched non-carriers from the autosomal dominant Alzheimer's disease kindred in Antioquia, Colombia. Plasma NfL measurements increased with age (p<0.0001), and began to differentiate carriers from non-carriers at 22 years. These results further confirm data from the Dominantly Inherited Alzheimer Network, in which a genetically heterogeneous population was tested, and from patients with sporadic Alzheimer's disease. However, blood NfL concentrations are non-specific, reflecting only underlying neuronal or axonal damage. In the preclinical and prodromal stages of Alzheimer's disease, blood NfL concentrations have limited use, but could yet prove valuable for monitoring the efficacy of interventions targeting the aggregation and accumulation of amyloid β.