Beyond Amyloid: Hippocampal Atrophy as a Prognostic Marker in Amyloid-Negative Subjective Cognitive Decline

Abstract

The emergence of blood-based biomarkers (BBMs) has transformed the diagnosis of Alzheimer’s disease (AD). 1,2 Plasma phosphorylated tau, glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) have demonstrated remarkable accuracy in detecting amyloid pathology and predicting disease progression across the AD spectrum. 1-3 An important question that arises as these biomarkers increasingly enter clinical practice is whether they retain prognostic value in individuals who lack cerebral amyloid pathology. In this issue of the Journal of Clinical Neurology , Yoon et al. 4 address this important knowledge gap by examining the comparative prognostic performance of plasma biomarkers and structural MRI markers in amyloid-negative subjective cognitive decline (A-SCD). Their study provides valuable insights into a clinically common but biologically heterogeneous population that remains poorly understood. 4