Performance of plasma Aβ42/40, measured using a fully automated immunoassay, across a broad patient population in identifying amyloid status
© 2023. BioMed Central Ltd., part of Springer Nature..
BACKGROUND: Plasma biomarkers have emerged as promising screening tools for Alzheimer's disease (AD) because of their potential to detect amyloid β (Aβ) accumulation in the brain. One such candidate is the plasma Aβ42/40 ratio (Aβ42/40). Unlike previous research that used traditional immunoassay, recent studies that measured plasma Aβ42/40 using fully automated platforms reported promising results. However, its utility should be confirmed using a broader patient population, focusing on the potential for early detection.
METHODS: We recruited 174 participants, including healthy controls (HC) and patients with clinical diagnoses of AD, frontotemporal lobar degeneration, dementia with Lewy bodies/Parkinson's disease, mild cognitive impairment (MCI), and others, from a university memory clinic. We examined the performance of plasma Aβ42/40, measured using the fully automated high-sensitivity chemiluminescence enzyme (HISCL) immunoassay, in detecting amyloid-positron emission tomography (PET)-derived Aβ pathology. We also compared its performance with that of Simoa-based plasma phosphorylated tau at residue 181 (p-tau181), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL).
RESULTS: Using the best cut-off derived from the Youden Index, plasma Aβ42/40 yielded an area under the receiver operating characteristic curve (AUC) of 0.949 in distinguishing visually assessed 18F-Florbetaben amyloid PET positivity. The plasma Aβ42/40 had a significantly superior AUC than p-tau181, GFAP, and NfL in the 167 participants with measurements for all four biomarkers. Next, we analyzed 99 participants, including only the HC and those with MCI, and discovered that plasma Aβ42/40 outperformed the other plasma biomarkers, suggesting its ability to detect early amyloid accumulation. Using the Centiloid scale (CL), Spearman's rank correlation coefficient between plasma Aβ42/40 and CL was -0.767. Among the 15 participants falling within the CL values indicative of potential future amyloid accumulation (CL between 13.5 and 35.7), plasma Aβ42/40 categorized 61.5% (8/13) as Aβ-positive, whereas visual assessment of amyloid PET identified 20% (3/15) as positive.
CONCLUSION: Plasma Aβ42/40 measured using the fully automated HISCL platform showed excellent performance in identifying Aβ accumulation in the brain in a well-characterized cohort. This equipment may be useful for screening amyloid pathology because it has the potential to detect early amyloid pathology and is readily applied in clinical settings.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
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| Enthalten in: |
Alzheimer's research & therapy - 15(2023), 1 vom: 04. Sept., Seite 149 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Bun, Shogyoku [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 06.09.2023 Date Revised 21.11.2023 published: Electronic UMIN-CTR: UMIN000032027 Citation Status MEDLINE |
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| doi: |
10.1186/s13195-023-01296-5 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM361651120 |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023. BioMed Central Ltd., part of Springer Nature. | ||
| 520 | |a BACKGROUND: Plasma biomarkers have emerged as promising screening tools for Alzheimer's disease (AD) because of their potential to detect amyloid β (Aβ) accumulation in the brain. One such candidate is the plasma Aβ42/40 ratio (Aβ42/40). Unlike previous research that used traditional immunoassay, recent studies that measured plasma Aβ42/40 using fully automated platforms reported promising results. However, its utility should be confirmed using a broader patient population, focusing on the potential for early detection | ||
| 520 | |a METHODS: We recruited 174 participants, including healthy controls (HC) and patients with clinical diagnoses of AD, frontotemporal lobar degeneration, dementia with Lewy bodies/Parkinson's disease, mild cognitive impairment (MCI), and others, from a university memory clinic. We examined the performance of plasma Aβ42/40, measured using the fully automated high-sensitivity chemiluminescence enzyme (HISCL) immunoassay, in detecting amyloid-positron emission tomography (PET)-derived Aβ pathology. We also compared its performance with that of Simoa-based plasma phosphorylated tau at residue 181 (p-tau181), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) | ||
| 520 | |a RESULTS: Using the best cut-off derived from the Youden Index, plasma Aβ42/40 yielded an area under the receiver operating characteristic curve (AUC) of 0.949 in distinguishing visually assessed 18F-Florbetaben amyloid PET positivity. The plasma Aβ42/40 had a significantly superior AUC than p-tau181, GFAP, and NfL in the 167 participants with measurements for all four biomarkers. Next, we analyzed 99 participants, including only the HC and those with MCI, and discovered that plasma Aβ42/40 outperformed the other plasma biomarkers, suggesting its ability to detect early amyloid accumulation. Using the Centiloid scale (CL), Spearman's rank correlation coefficient between plasma Aβ42/40 and CL was -0.767. Among the 15 participants falling within the CL values indicative of potential future amyloid accumulation (CL between 13.5 and 35.7), plasma Aβ42/40 categorized 61.5% (8/13) as Aβ-positive, whereas visual assessment of amyloid PET identified 20% (3/15) as positive | ||
| 520 | |a CONCLUSION: Plasma Aβ42/40 measured using the fully automated HISCL platform showed excellent performance in identifying Aβ accumulation in the brain in a well-characterized cohort. This equipment may be useful for screening amyloid pathology because it has the potential to detect early amyloid pathology and is readily applied in clinical settings | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a Alzheimer’s disease | |
| 650 | 4 | |a Amyloid positron emission tomography | |
| 650 | 4 | |a Amyloid β | |
| 650 | 4 | |a Centiloid | |
| 650 | 4 | |a Plasma Aβ42/40 | |
| 650 | 7 | |a amyloid beta-protein (1-42) |2 NLM | |
| 650 | 7 | |a Amyloid beta-Peptides |2 NLM | |
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| 700 | 1 | |a Ueda, Ryo |e verfasserin |4 aut | |
| 700 | 1 | |a Takahata, Keisuke |e verfasserin |4 aut | |
| 700 | 1 | |a Moriguchi, Sho |e verfasserin |4 aut | |
| 700 | 1 | |a Kurose, Shin |e verfasserin |4 aut | |
| 700 | 1 | |a Momota, Yuki |e verfasserin |4 aut | |
| 700 | 1 | |a Suzuki, Natsumi |e verfasserin |4 aut | |
| 700 | 1 | |a Morimoto, Ayaka |e verfasserin |4 aut | |
| 700 | 1 | |a Hoshino, Yuka |e verfasserin |4 aut | |
| 700 | 1 | |a Seki, Morinobu |e verfasserin |4 aut | |
| 700 | 1 | |a Mimura, Yu |e verfasserin |4 aut | |
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| 700 | 1 | |a Sato, Yoshiaki |e verfasserin |4 aut | |
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| 700 | 1 | |a Mimura, Masaru |e verfasserin |4 aut | |
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