Quantifying natural amyloid plaque accumulation in the continuum of Alzheimer's disease using ADNI.

IF 2.2 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Marwa E Elhefnawy, Noel Patson, Samer Mouksassi, Goonaseelan Pillai, Sergey Shcherbinin, Emmanuel Chigutsa, Ivelina Gueorguieva
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引用次数: 0

Abstract

Brain amyloid beta neuritic plaque accumulation is associated with an increased risk of progression to Alzheimer's disease (AD) [Pfeil, J., et al. in Neurobiol Aging 106: 119-129, 2021]. Several studies estimate rates of change in amyloid plaque over time in clinically heterogeneous cohorts with different factors impacting amyloid plaque accumulation from ADNI and AIBL [Laccarino, L., et al. in Annals Clin and Trans Neurol 6: 1113 1120, 2019, Vos, S.J., et al. in Brain 138: 1327-1338, 2015, Lim, Y.Y., et al. in Alzheimer's Dementia 9: 538-545, 2013], but there are no reports using non-linear mixed effect model for amyloid plaque progression over time similar to that existing of disease-modifying biomarkers for other diseases [Cook, S.F. and R.R. Bies in Current Pharmacol Rep 2: 221-230, 2016, Gueorguieva, I., et al. in Alzheimer's Dementia 19: 2253-2264, 2023]. This study describes the natural progression of amyloid accumulation with population mean and between-participant variability for baseline and intrinsic progression rates quantified across the AD spectrum. 1340 ADNI participants were followed over a 10-year period with 18F-florbetapir PET scans used for amyloid plaque detection. Non-linear mixed effect with stepwise covariate modelling (scm) was used. Change in natural amyloid plaque levels over 10 year period followed an exponential growth model with an intrinsic rate of approx. 3 centiloid units/year. Age, gender, APOE4 genotype and disease stage were important factors on the baseline in the natural amyloid model. In APOE4 homozygous carriers mean baseline amyloid was increased compared to APOE4 non carriers. These results demonstrate natural progression of amyloid plaque in the continuum of AD.

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来源期刊
CiteScore
4.90
自引率
4.00%
发文量
39
审稿时长
6-12 weeks
期刊介绍: Broadly speaking, the Journal of Pharmacokinetics and Pharmacodynamics covers the area of pharmacometrics. The journal is devoted to illustrating the importance of pharmacokinetics, pharmacodynamics, and pharmacometrics in drug development, clinical care, and the understanding of drug action. The journal publishes on a variety of topics related to pharmacometrics, including, but not limited to, clinical, experimental, and theoretical papers examining the kinetics of drug disposition and effects of drug action in humans, animals, in vitro, or in silico; modeling and simulation methodology, including optimal design; precision medicine; systems pharmacology; and mathematical pharmacology (including computational biology, bioengineering, and biophysics related to pharmacology, pharmacokinetics, orpharmacodynamics). Clinical papers that include population pharmacokinetic-pharmacodynamic relationships are welcome. The journal actively invites and promotes up-and-coming areas of pharmacometric research, such as real-world evidence, quality of life analyses, and artificial intelligence. The Journal of Pharmacokinetics and Pharmacodynamics is an official journal of the International Society of Pharmacometrics.
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