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

ABSTRACT: 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 ? (A?)1-40, A?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 A?1-42 levels than amyloid PET-negative (PET-) subjects. APOE ?4 carriers had higher plasma A?1-42 than non-carriers. We developed an algorithm involving the combination of plasma A?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 A?1-42 levels as a pre-screening tool for predicting the positivity of amyloid PET findings in early stage dementia patients.

SUBMITTER: Lin SY

PROVIDER: S-EPMC6933740 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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

Lin Szu-Ying SY Lin Kun-Ju KJ Lin Po-Chen PC Huang Chin-Chang CC Chang Chiung-Chih CC Lee Yi-Chung YC Hsiao Ing-Tsung IT Yen Tzu-Chen TC Huang Wen-Sheng WS Yang Bang-Hung BH Wang Pei-Ning PN

Alzheimer's research & therapy 20191227 1

<h4>Introduction</h4>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.<h4>Methods</h4>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 imagin ...[more]

PMID: 31881963

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Project description:BackgroundRecognizing clinical manifestations heralding the development of Alzheimer's disease (AD)-related cognitive impairment could improve the identification of individuals at higher risk of AD who may benefit from potential prevention strategies targeting preclinical population. We aim to characterize the association of body weight change with cognitive changes and AD biomarkers in cognitively unimpaired middle-aged adults.MethodsThis prospective cohort study included data from cognitively unimpaired adults from the ALFA study (n?=?2743), a research platform focused on preclinical AD. Cognitive and anthropometric data were collected at baseline between April 2013 and November 2014. Between October 2016 and February 2020, 450 participants were visited in the context of the nested ALFA+ study and underwent cerebrospinal fluid (CSF) extraction and acquisition of positron emission tomography images with [18F]flutemetamol (FTM-PET). From these, 408 (90.1%) were included in the present study. We used data from two visits (average interval 4.1?years) to compute rates of change in weight and cognitive performance. We tested associations between these variables and between weight change and categorical and continuous measures of CSF and neuroimaging AD biomarkers obtained at follow-up. We classified participants with CSF data according to the AT (amyloid, tau) system and assessed between-group differences in weight change.ResultsWeight loss predicted a higher likelihood of positive FTM-PET visual read (OR 1.27, 95% CI 1.00-1.61, p?=?0.049), abnormal CSF p-tau levels (OR 1.50, 95% CI 1.19-1.89, p?=?0.001), and an A+T+ profile (OR 1.64, 95% CI 1.25-2.20, p?=?0.001) and was greater among participants with an A+T+ profile (p?<?0.01) at follow-up. Weight change was positively associated with CSF A?42/40 ratio (??=?0.099, p?=?0.032) and negatively associated with CSF p-tau (??=?-?0.141, p?=?0.005), t-tau (??=?-?0.147 p?=?0.004) and neurogranin levels (??=?-?0.158, p?=?0.002). In stratified analyses, weight loss was significantly associated with higher t-tau, p-tau, neurofilament light, and neurogranin, as well as faster cognitive decline in A+ participants only.ConclusionsWeight loss predicts AD CSF and PET biomarker results and may occur downstream to amyloid-? accumulation in preclinical AD, paralleling cognitive decline. Accordingly, it should be considered as an indicator of increased risk of AD-related cognitive impairment.Trial registrationNCT01835717 , NCT02485730 , NCT02685969 .

Project description:Positron emission tomography (PET) is an imaging technology that measures the concentration, distribution, and pharmacokinetics of radiotracers-molecules that are labeled with short-lived positron-emitting variants of chemical elements naturally found in the body. These radioisotopes can be attached to compounds involved in normal brain function and then injected into the blood stream. The signals emitted by these radiotracers then are measured using specific detectors. PET is a highly sensitive method; it measures radioisotope concentrations in the nanomolar to picomolar range (10-9 to 10-12 M) . Therefore, the technique can be used to label compounds that are of pharmacological and physiological relevance. These radiotracers then can be used to probe neurochemical and metabolic processes at the relevant physiological concentrations without perturbing the system that is measured. To exert their effects on the brain, alcohol and other drugs (AODs) act on signaling molecules (i.e., neurotransmitters) in the brain as well as on the molecules on the surface of neurons (i.e., receptors) with which the neurotransmitters interact. Specific compounds that selectively bind to such receptors, to the molecules that transport neurotransmitters back into cells, and to the enzymes that are involved in the synthesis or metabolism of neurotransmitters can be labeled for use as PET radiotracers. As a result, PET can be used to assess the metabolic and neurochemical actions of AODs and to evaluate the consequences of chronic AOD use. Since its inception, PET has been used extensively to study the effects of AODs in human and nonhuman primates; however, the recent development of microPET technology has expanded its applications to research in rodents. In addition, increasing numbers of studies are using PET methodology to assess the involvement of genetic variations in individual genes (i.e., polymorphisms) in brain function and neurochemistry. The studies discussed are divided into those that assess the effects of alcohol on brain function (i.e., brain metabolism and cerebral blood flow) and those that assess the effects of alcohol on brain function (i.e., brain metabolism and cerebral blood flow) and those that assess its effects on neurochemistry.

Dataset Information

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

Publications

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

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