Nanoscale flow cytometry-based quantification of blood-based extracellular vesicle biomarkers distinguishes MCI and Alzheimer's disease

被引：4

作者：

Dayarathna, Thamara ^{[1
]}

Roseborough, Austyn D. ^{[2
]}

Gomes, Janice ^{[3
]}

Khazaee, Reza ^{[4
,5
]}

Silveira, Carolina R. A. ^{[6
]}

Borron, Kathy ^{[6
]}

Yu, Soojung ^{[6
]}

Coleman, Kristy ^{[6
]}

Jesso, Sarah ^{[6
]}

Finger, Elizabeth ^{[3
,6
,7
]}

MacDonald, Penny ^{[7
]}

Borrie, Michael ^{[8
]}

Wells, Jennie ^{[8
]}

Bartha, Robert ^{[3
]}

Zou, Guangyong ^{[3
,9
]}

Whitehead, Shawn N. ^{[2
]}

Leong, Hon S. ^{[10
]}

Pasternak, Stephen H. ^{[3
,6
,7
]}

机构：

[1] Nationwide Childrens Hosp, Abigail Wexner Res Inst, Inst Genom Med, Columbus, OH USA

[2] Western Univ, Schulich Sch Med & Dent, Dept Anat & Cell Biol, Vulnerable Brain Lab, London, ON, Canada

[3] Western Univ, Robarts Res Inst, Schulich Sch Med & Dent, London, ON, Canada

[4] Western Univ, Dept Biol, London, ON, Canada

[5] Western Univ, Biotron Integrated Microscopy Facil, London, ON, Canada

[6] St Josephs Hlth Care Ctr, Parkwood Inst, Cognit Neurol & Alzheimers Dis Res Ctr, London, ON, Canada

[7] Western Univ, Schulich Sch Med & Dent, Dept Clin Neurol Sci, London, ON, Canada

[8] Western Univ, Schulich Sch Med & Dent, Dept Geriatr Med, London, ON, Canada

[9] Western Univ, Schulich Sch Med & Dent, Dept Epidemiol & Biostat, London, ON, Canada

[10] Univ Toronto, Sunnybrook Res Inst, Toronto, ON, Canada

来源：

ALZHEIMERS & DEMENTIA | 2024年 / 20卷 / 09期

关键词：

Alzheimer's disease; biomarker; dementia; extracellular vesicle; mild cognitive impairment; nanoflow cytometry; MILD COGNITIVE IMPAIRMENT; NEURONAL EXOSOMES; ALPHA-SYNUCLEIN; PHASE-3; TRIALS; PROTEINS; PLASMA; DIAGNOSIS; BAPINEUZUMAB; SOLANEZUMAB;

D O I：

10.1002/alz.14087

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

INTRODUCTION: Accurate testing for Alzheimer's disease (AD) represents a crucial step for therapeutic advancement. Currently, tests are expensive and require invasive sampling or radiation exposure. METHODS: We developed a nanoscale flow cytometry (nFC)-based assay of extracellular vesicles (EVs) to screen biomarkers in plasma from mild cognitive impairment (MCI), AD, or controls. RESULTS: Circulating amyloid beta (A beta), tau, phosphorylated tau (p-tau)181, p-tau231, p-tau217, p-tauS235, ubiquitin, and lysosomal-associated membrane protein 1-positive EVs distinguished AD samples. p-tau181, p-tau217, p-tauS235, and ubiquitin-positive EVs distinguished MCI samples. The most sensitive marker for AD distinction was p-tau231, with an area under the receiver operating characteristic curve (AUC) of 0.96 (sensitivity 0.95/specificity 1.0) improving to an AUC of 0.989 when combined with p-tauS235. DISCUSSION: This nFC-based assay accurately distinguishes MCI and AD plasma without EV isolation, offering a rapid approach requiring minute sample volumes. Incorporating nFC-based measurements in larger populations and comparison to "gold standard" biomarkers is an exciting next step for developing AD diagnostic tools.

引用

页码：6094 / 6106

页数：13

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