AUTHOR=Li Kaicheng , Fu Zening , Qi Shile , Luo Xiao , Zeng Qingze , Xu Xiaopei , Huang Peiyu , Zhang Minming , Calhoun Vince D. 

TITLE=Polygenic Hazard Score Associated Multimodal Brain Networks Along the Alzheimer’s Disease Continuum

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=Volume 13 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2021.725246

DOI=10.3389/fnagi.2021.725246

ISSN=1663-4365

ABSTRACT=Background: Late-onset Alzheimer's disease (AD) is a polygenic neurodegenerative disease. Identifying the neuroimaging phenotypes behind the genetic predisposition of AD is critical to the understanding of AD pathogenesis. Two major questions which previous studies have led to are: 1) should the general 'polygenic hazard score' (PHS) be a better choice to identify the individual genetic risk for AD instead of any single genetic variant; and 2) should researchers also include inter-modality relationships in the analyses considering these may provide complementary information about the AD etiology. 
Methods: We collected 88 healthy controls, 77 patients with mild cognitive impairment (MCI), and 22 AD patients to simulate the AD continuum. PHS-guided multimodal fusion was used to investigate the impact of PHS on multimodal brain networks in AD-continuum by maximizing both inter-modality association and reference-modality correlation. Fractional amplitude of low frequency fluctuations, gray matter volume, and amyloid standard uptake value ratios were included as neuroimaging features. Eventually, the changes in neuroimaging features along AD continuum were investigated, and relationships between cognitive performance and identified PHS associated multimodal components were established. 
Results: We found that PHS was associated with multimodal brain networks, which showed different functional and structural impairments under increased amyloid deposits. Notably, along with AD progression, functional impairment occurred before neurodegeneration, amyloid deposition started from the MCI stage and progressively increased throughout the disease continuum. 
Conclusions: PHS is associated with multi-facets of brain impairments along the AD continuum, including cognitive dysfunction, pathological deposition, and neurodegeneration, which might underpin the AD pathogenesis.