A simple genetic stratification method for lower cost, more expedient clinical trials in early Alzheimer's disease: A preliminary study of tau PET and cognitive outcomes
- 26 January 2023
- journal article
- research article
- Published by Wiley in Alzheimer's & Dementia
- Vol. 19 (7), 3078-3086
- https://doi.org/10.1002/alz.12952
Abstract
IntroductionIdentifying individuals who are most likely to accumulate tau and exhibit cognitive decline is critical for Alzheimer's disease (AD) clinical trials. MethodsParticipants (N = 235) who were cognitively normal or with mild cognitive impairment from the Alzheimer's Disease Neuroimaging Initiative were stratified by a cutoff on the polygenic hazard score (PHS) at 65th percentile (above as high-risk group and below as low-risk group). We evaluated the associations between the PHS risk groups and tau positron emission tomography and cognitive decline, respectively. Power analyses estimated the sample size needed for clinical trials to detect differences in tau accumulation or cognitive change. ResultsThe high-risk group showed faster tau accumulation and cognitive decline. Clinical trials using the high-risk group would require a fraction of the sample size as trials without this inclusion criterion. DiscussionIncorporating a PHS inclusion criterion represents a low-cost and accessible way to identify potential participants for AD clinical trials.Funding Information
- National Institutes of Health (1R01AG066088, U01 AG024904)
This publication has 41 references indexed in Scilit:
- [F‐18]AV‐1451 positron emission tomography retention in choroid plexus: More than “off‐target” bindingAnnals of Neurology, 2016
- Analysis of the MIRIAD Data Shows Sex Differences in Hippocampal Atrophy ProgressionJournal of Alzheimer's Disease, 2016
- Tau positron emission tomographic imaging in aging and early Alzheimer diseaseAnnals of Neurology, 2015
- The National Institute on Aging Health Disparities Research FrameworkEthnicity & Disease, 2015
- AD genetic risk factors and tau spreadingFrontiers in Aging Neuroscience, 2015
- Models of β-amyloid induced Tau-pathology: the long and “folded” road to understand the mechanismMolecular Neurodegeneration, 2014
- Amyloid-β and TauJAMA Neurology, 2014
- Deletion of Crry, the murine ortholog of the sporadic Alzheimer's disease risk gene CR1, impacts tau phosphorylation and brain CFHNeuroscience Letters, 2013
- Aβ Accelerates the Spatiotemporal Progression of Tau Pathology and Augments Tau Amyloidosis in an Alzheimer Mouse ModelThe American Journal of Pathology, 2010
- Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer's diseaseNeurology, 1992