Abstract
INTRODUCTION: While amyloid cerebrospinal fluid (CSF) and positron emission tomography (PET) biomarkers are considered interchangeable indicators of Alzheimer's disease (AD) pathology, biomarker discrepancies can occur but remain poorly characterized. METHODS: We evaluated (18)F-florbetapir amyloid PET, (18)F-Florzolotau PET (tau pathology), magnetic resonance imaging (MRI) findings, and CSF biomarkers in a 59-year-old man carrying the pathogenic APP p.K687Q mutation, who presented with possible corticobasal syndrome. RESULTS: CSF analysis revealed reduced amyloid beta (Aβ)(1-42) (503.44 pg/mL) and Aβ(1-42)/Aβ(1-40) ratio (0.044), indicating amyloid pathology. Conversely, (18)F-florbetapir PET was visually negative (standardized uptake value ratio [SUVR] 0.97; -11.8 Centiloids). (18)F-Florzolotau PET demonstrated AD-typical tau deposition, whereas MRI revealed extensive white matter hyperintensities, enlarged perivascular spaces, and a temporal microbleed. DISCUSSION: The observed discordance suggests that CSF and PET amyloid biomarkers can diverge in certain patients. Potential mechanisms include polymorphic Aβ fibrils lacking (18)F-florbetapir binding sites, excess non-fibrillar aggregates, low fibril density, or contributions from cerebral amyloid angiopathy. HIGHLIGHTS: CSF Aβ and (18)F-florbetapir PET findings showed a mismatch in a patient with an APP mutation. Amyloid pathology should not be excluded despite negative (18)F-florbetapir PET findings. Mismatch may reflect altered ligand binding or fibril structural variants. Comorbid cerebral amyloid angiopathy may contribute to biomarker discrepancies.