Discordant cerebrospinal fluid and positron emission tomography amyloid biomarkers in an APP mutation carrier presenting corticobasal syndrome

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 ¹⁸F-florbetapir amyloid PET, ¹⁸F-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, ¹⁸F-florbetapir PET was visually negative (standardized uptake value ratio [SUVR] 0.97; −11.8 Centiloids). ¹⁸F-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 ¹⁸F-florbetapir binding sites, excess non-fibrillar aggregates, low fibril density, or contributions from cerebral amyloid angiopathy.

Highlights

• CSF Aβ and ¹⁸F-florbetapir PET findings showed a mismatch in a patient with an APP mutation.
• Amyloid pathology should not be excluded despite negative ¹⁸F-florbetapir PET findings.
• Mismatch may reflect altered ligand binding or fibril structural variants.
• Comorbid cerebral amyloid angiopathy may contribute to biomarker discrepancies.