Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Jul;19(7):3078-3086.
doi: 10.1002/alz.12952. Epub 2023 Jan 26.

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

Xin Wang  1 , Iris Broce  1 , Yuqi Qiu  2 , Kacie D Deters  3 , Chun Chieh Fan  1 , Anders M Dale  1 , Steven D Edland  1 , Sarah J Banks  1 ; Alzheimer's Disease Neuroimaging Initiative
Affiliations

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

Xin Wang et al. Alzheimers Dement. 2023 Jul.

Abstract

Introduction: Identifying individuals who are most likely to accumulate tau and exhibit cognitive decline is critical for Alzheimer's disease (AD) clinical trials.

Methods: Participants (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.

Results: The 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.

Discussion: Incorporating a PHS inclusion criterion represents a low-cost and accessible way to identify potential participants for AD clinical trials.

Keywords: Alzheimer's disease; clinical trials; polygenic hazard score; tau positron emission tomography.

PubMed Disclaimer

Conflict of interest statement

CONFLICTS OF INTEREST

Xin Wang, Iris Broce, Yuqi Qiu, Kacie D. Deters, Chun Chieh Fan, Anders M. Dale, Steven D. Edland, and Sarah J. Banks have no relevant disclosures for this paper.

Figures

FIGURE 1
FIGURE 1
PHS risk groups by tau PET in ROIs interaction on cognitive decline rates. PET, positron emission tomography; PHS, polygenic hazard score; ROIs, regions of interest; SUVR, standardized uptake volume ratio
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Yiannopoulou KG, Anastasiou AI, Zachariou V, Pelidou SH. Reasons for failed trials of disease-modifying treatments for Alzheimer disease and their contribution in recent research. Biomedicines. 2019;7:97. - PMC - PubMed
    1. Tan CH, Hyman BT, Tan JJX, et al. Polygenic hazard scores in preclinical Alzheimer disease. Ann Neurol. 2017;82:484–488. - PMC - PubMed
    1. Tan CH, Fan CC, Mormino EC, et al. Polygenic hazard score: an enrichment marker for Alzheimer’s associated amyloid and tau deposition. Acta Neuropathol. 2018;135:85–93. - PMC - PubMed
    1. Kametani F, Hasegawa M. Reconsideration of amyloid hypothesis and tau hypothesis in Alzheimer’s disease. Front Neurosci. 2018;12:25. - PMC - PubMed
    1. Congdon EE, Sigurdsson EM. Tau-targeting therapies for Alzheimer disease. Nat Rev Neurol. 2018;14:399–415. - PMC - PubMed

Publication types