Plasma amyloid assay as a pre-screening tool for amyloid positron emission tomography imaging in early stage Alzheimer’s disease

• Published in: Alzheimer's research & therapy Vol. 11; no. 1; pp. 111 - 10
• Main Authors: Lin, Szu-Ying, Lin, Kun-Ju, Lin, Po-Chen, Huang, Chin-Chang, Chang, Chiung-Chih, Lee, Yi-Chung, Hsiao, Ing-Tsung, Yen, Tzu-Chen, Huang, Wen-Sheng, Yang, Bang-Hung, Wang, Pei-Ning
• Format: Journal Article
• Language: English
• Published: London BioMed Central 27.12.2019; BioMed Central Ltd; BMC
• Subjects: Accuracy; Advertising executives; Algorithms; Alzheimer's disease; Amyloid PET; APOE; Apolipoproteins; Biological markers; Biomarkers; Biomedical and Life Sciences; Biomedicine; Brain; Cognitive ability; Dementia; Diagnostic imaging; Disease; EDTA; Florbetapir; Genotypes; Geriatric Psychiatry; Geriatrics/Gerontology; Laboratories; MCI; Medical imaging; Medical research; Medical tests; Neurology; Neurosciences; Pathology; Plasma Aβ; Positron emission tomography; Proteins; Tomography; Taiwan; Plasma Aβ; Biomarkers; MCI; AD; Amyloid PET; APOE
• ISSN: 1758-9193; 1758-9193
• DOI: 10.1186/s13195-019-0566-0

Introduction Due to the high cost and high failure rate of ascertaining amyloid positron emission tomography positivity (PET+) in patients with earlier stage Alzheimer’s disease (AD), an effective pre-screening tool for amyloid PET scans is needed. Methods Patients with mild cognitive impairment ( n  = 33, 24.2% PET+, 42% females, age 74.4 ± 7.5, MMSE 26.8 ± 1.9) and mild dementia ( n  = 19, 63.6% PET+, 36.3% females, age 73.0 ± 9.3, MMSE 22.6 ± 2.0) were recruited. Amyloid PET imaging, Apolipoprotein E ( APOE ) genotyping, and plasma amyloid β (Aβ) 1–40 , Aβ 1–42 , and total tau protein quantification by immunomagnetic reduction (IMR) method were performed. Receiver operating characteristics (ROC) analysis and Youden’s index were performed to identify possible cut-off points, clinical sensitivities/specificities, and areas under the curve (AUCs). Results Amyloid PET+ participants had lower plasma Aβ 1–42 levels than amyloid PET-negative (PET−) subjects. APOE ε4 carriers had higher plasma Aβ 1–42 than non-carriers. We developed an algorithm involving the combination of plasma Aβ 1–42 and APOE genotyping. The success rate for detecting amyloid PET+ patients effectively increased from 42.3 to 70.4% among clinically suspected MCI and mild dementia patients. Conclusions Our results demonstrate the possibility of utilizing APOE genotypes in combination with plasma Aβ 1–42 levels as a pre-screening tool for predicting the positivity of amyloid PET findings in early stage dementia patients.