呈现皮质基底综合征的APP突变携带者的脑脊液和正电子发射断层扫描淀粉样蛋白生物标志物不一致

IF 11.1 1区医学 Q1 CLINICAL NEUROLOGY

Alzheimer's & Dementia Pub Date : 2025-10-21 DOI:10.1002/alz.70823

Feng-Tao Liu, Xin-Yi Li, Jia-Ying Lu, Chuan-Tao Zuo

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引用次数: 0

摘要

虽然淀粉样脑脊液（CSF）和正电子发射断层扫描（PET）生物标志物被认为是阿尔茨海默病（AD）病理的可互换指标，但生物标志物可能存在差异，但仍然缺乏特征。方法：我们评估了一名携带致病性APP p.K687Q突变的59岁男性的18F-florbetapir淀粉样蛋白PET、18F-Florzolotau PET （tau病理学）、磁共振成像（MRI）结果和脑脊液生物标志物，该患者可能表现为皮质基底综合征。结果：脑脊液分析显示淀粉样蛋白β (Aβ)1-42降低（503.44 pg/mL）， Aβ1-42/Aβ1-40比值降低（0.044），提示淀粉样蛋白病变。相反，18F-florbetapir PET在视觉上呈阴性（标准化摄取值比[SUVR] 0.97; -11.8 Centiloids）。18F-Florzolotau PET显示ad典型的tau沉积，而MRI显示广泛的白质高信号，血管周围空间扩大，颞部微出血。讨论：观察到的不一致表明CSF和PET淀粉样蛋白生物标志物在某些患者中可能存在分歧。潜在的机制包括多态的Aβ原纤维缺乏18F-florbetapir结合位点，过量的非纤维聚集物，低纤维密度或脑淀粉样血管病的贡献。亮点：脑脊液a β和18F-florbetapir PET结果显示APP突变患者不匹配。尽管18F-florbetapir PET结果为阴性，淀粉样蛋白病理学不应排除。不匹配可能反映了配体结合的改变或纤维结构的变异。共病性脑淀粉样血管病可能导致生物标志物差异。

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

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

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.

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来源期刊

Alzheimer's & Dementia 医学-临床神经学

CiteScore

14.50

自引率

5.00%

发文量

299

审稿时长

3 months

期刊介绍： Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.