Abstract
IntroductionDue 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.MethodsPatients 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, Aβ1–42, 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).ResultsAmyloid PET+ participants had lower plasma Aβ1–42 levels than amyloid PET-negative (PET−) subjects. APOE ε4 carriers had higher plasma Aβ1–42 than non-carriers. We developed an algorithm involving the combination of plasma Aβ1–42 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.ConclusionsOur results demonstrate the possibility of utilizing APOE genotypes in combination with plasma Aβ1–42 levels as a pre-screening tool for predicting the positivity of amyloid PET findings in early stage dementia patients.
Highlights
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
The plasma Aβ1–42/Aβ1–40 ratio increases with increasing amyloid load, as assessed by amyloid PET imaging in normal subjects and patients with dementia due to AD [28]. These results show the feasibility of assaying plasma Aβ1–42 and Aβ1–40 for evaluating whether to perform amyloid PET scans
Amyloid PET results According to visual rating of amyloid PET images, 22 of 52 (42.3%) subjects were amyloid PET+
Summary
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. Beta-amyloid (Aβ) plaque deposition in the brain is the pathological hallmark of Alzheimer’s disease (AD) [1,2,3]. Disease-modifying drugs with anti-amyloid effects are designed to eliminate aggregated Aβ [4,5,6]. The results of phase I and phase II trials of these anti-amyloid drugs reveal their ability to eliminate Aβ plaques in the brains of patients with prodromal AD [7,8,9]. To prove the efficacy of these drugs, trials target prodromal AD patients with. Cerebrospinal fluid (CSF) biomarkers are an alternative way to diagnose cerebral Aβ pathology. Many studies showed that the Aβ1–42 concentration in the CSF decreases in patients with dementia due to AD [14,15,16,17].
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