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. 2022 Mar:2022:10.1109/isbi52829.2022.9761576.
doi: 10.1109/isbi52829.2022.9761576. Epub 2022 Apr 26.

INVESTIGATING THE EFFECT OF TAU DEPOSITION AND APOE ON HIPPOCAMPAL MORPHOMETRY IN ALZHEIMER'S DISEASE: A FEDERATED CHOW TEST MODEL

Jianfeng Wu  1 , Yi Su  2 , Eric M Reiman  2 , Richard J Caselli  3 , Kewei Chen  2 , Paul M Thompson  4 , Junwen Wang  5 , Yalin Wang  1
Affiliations

INVESTIGATING THE EFFECT OF TAU DEPOSITION AND APOE ON HIPPOCAMPAL MORPHOMETRY IN ALZHEIMER'S DISEASE: A FEDERATED CHOW TEST MODEL

Jianfeng Wu et al. Proc IEEE Int Symp Biomed Imaging. 2022 Mar.

Abstract

Alzheimer's disease (AD) affects more than 1 in 9 people age 65 and older and becomes an urgent public health concern as the global population ages. Tau tangle is the specific protein pathological hallmark of AD and plays a crucial role in leading to dementia-related structural deformations observed in magnetic resonance imaging (MRI) scans. The volume loss of hippocampus is mainly related to the development of AD. Besides, apolipoprotein E (APOE) also has significant effects on the risk of developing AD. However, few studies focus on integrating genotypes, MRI, and tau deposition to infer multimodal relationships. In this paper, we proposed a federated chow test model to study the synergistic effects of APOE and tau on hippocampal morphometry. Our experimental results demonstrate our model can detect the difference of tau deposition and hippocampal atrophy among the cohorts with different genotypes and subiculum and cornu ammonis 1 (CA1 subfield) were identified as hippocampal subregions where atrophy is strongly associated with abnormal tau in the homozygote cohort. Our model will provide novel insight into the neural mechanisms about the individual impact of APOE and tau deposition on brain imaging.

Keywords: APOE; Alzheimer’s Disease; Hippocampal Morphometry; federated chow test; tau deposition.

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Figures

Fig. 1.
Fig. 1.. The intuition of our multi-omics approach.
The image-tau relationship (correlation) is diluted when the population is mixed, but when we stratify the population based on their genotypes, we can observe strong correlations (AA and BB) across subgroups.
Fig. 2.
Fig. 2.. Framework of chow test model.
The samples are stratified into three cohorts according to their APOE genotypes. Each imaging biomarker is used as the predicter and the measure for tau is used as the response.
Fig. 3.
Fig. 3.. Correlation of hippocampal volume and Braak34 in subpopulations stratified by the sample’s APOE genotype.
The top four subfigures are the distributions for left hippocampal volume and Braak34 and the bottom four are for right hippocampus and Braak34. The first column is the results for all the 847 samples and the rest are for the cohorts of NC, HT and HM, respectively. R and p are Pearson correlation coefficient and p-value.
Fig. 4.
Fig. 4.. p-maps of our federated chow test model.
The warmer color regions have more significant p-values. The top two subfigures are the results for RD and the bottom two are for TBM.
Fig. 5.
Fig. 5.
Cumulative distribution functions of the p-values.
See this image and copyright information in PMC

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