Exp Neurobiol.  2025 Feb;34(1):1-8. 10.5607/en25008.

Combination of Aβ40, Aβ42, and Tau Plasma Levels to Distinguish Amyloid-PET Positive Alzheimer Patients from Normal Controls

Affiliations
  • 1Department of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, College of Pharmacy, Yonsei University, Incheon 21983, Korea
  • 2Department of Nuclear Medicine, Korea Cancer Center Hospital, Seoul 01812, Korea
  • 3Department of Neurology, Korea Cancer Center Hospital, Seoul 01812, Korea
  • 4Division of RI-Convergence Research, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Korea
  • 5Department of Medical Biotechnology, Dongguk University, Seoul 04620, Korea
  • 6Department of Pharmacology, Korea University, Seoul 02841, Korea
  • 7Pharmaceutical Sciences Division and Wisconsin Center for NanoBioSystems (WisCNano), School of Pharmacy, University of Wisconsin, Madison, WI 53705, USA
  • 8Department of Biotechnology, Yonsei University, Seoul 03722, Korea
  • 9Amyloid Solution Inc., Seongnam 13486, Korea

Abstract

Alzheimer disease (AD) diagnosis is confirmed using a medley of modalities, such as the detection of amyloid-β (Aβ) neuritic plaques and neurofibrillary tangles with positron electron tomography (PET) or the appraisal of irregularities in cognitive function with examinations. Although these methods have been efficient in confirming AD pathology, the rising demand for earlier intervention during pathogenesis has led researchers to explore the diagnostic potential of fluid biomarkers in cerebrospinal fluid (CSF) and plasma. Since CSF sample collection is invasive and limited in quantity, biomarker detection in plasma has become more attractive and modern advancements in technology has permitted more efficient and accurate analysis of plasma biomolecules. In this study, we found that a composite of standard factors, Aβ40 and total tau levels in plasma, divided by the variation factor, plasma Aβ42 level, provide better correlation with amyloid neuroimaging and neuropsychological test results than a level comparison between total tau and Aβ42 in plasma. We collected EDTA-treated blood plasma samples of 53 subjects, of randomly selected 27 AD patients and 26 normal cognition (NC) individuals, who received amyloid-PET scans for plaque quantification, and measured plasma levels of Aβ40, Aβ42, and total tau with digital enzyme-linked immunosorbent assay (ELISA) in a blinded manner. There was difficulty distinguishing AD patients from controls when analyzing biomarkers independently. However, significant differentiation was observed between the two groups when comparing individual ratios of total-tau×Aβ40/Aβ42. Our results indicate that collectively comparing fluctuations of these fluid biomarkers could aid in monitoring AD pathogenesis.

Keyword

Alzheimer disease; Amyloid, Tau; Plasma; Blood; Enzyme-linked immunosorbent assay
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