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

## TL;DR

A patient with an APP mutation showed conflicting amyloid biomarker results between cerebrospinal fluid and PET scans, suggesting limitations in using these markers interchangeably.

## Contribution

This case highlights discordance between CSF and PET amyloid biomarkers in an APP mutation carrier, offering insights into potential mechanisms of biomarker mismatch.

## Key findings

- CSF showed amyloid pathology with low Aβ1-42 and Aβ1-42/Aβ1-40 ratio, while 18F-florbetapir PET was visually negative.
- 18F-Florzolotau PET showed AD-typical tau deposition, and MRI revealed white matter hyperintensities and microbleeds.
- Biomarker discrepancies may stem from altered ligand binding, fibril structure variants, or cerebral amyloid angiopathy.

## Abstract

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.

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.

CSF analysis revealed reduced amyloid beta (Aβ)1‐42 (503.44 pg/mL) and Aβ1‐42/Aβ1‐40 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.

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.

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.

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.