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Association Between Polygenic Risk Score and the Progression from Mild Cognitive Impairment to Alzheimer's Disease.

Publication ,  Journal Article
Liu, H; Lutz, M; Luo, S; Alzheimer’s Disease Neuroimaging Initiative,
Published in: J Alzheimers Dis
2021

BACKGROUND: Mild cognitive impairment (MCI) is a heterogeneous condition and MCI patients are at increased risk of progression to dementia due to Alzheimer's disease (AD). OBJECTIVE: In this study, we aim to evaluate the associations between polygenic risk scores (PRSs) and 1) time to AD progression from MCI, 2) changes in longitudinal cognitive impairment, and 3) biomarkers from cerebrospinal fluid and imaging. METHODS: We constructed PRS by using 40 independent non-APOE SNPs from well-replicated AD GWASs and tested its association with the progression time from MCI to AD by using 767 MCI patients from the ADNI study and 1373 patients from the NACC study. PRSs calculated with other methods were also computed. RESULTS: We found that the PRS constructed with SNPs that reached genome-wide significance predicted the progression from MCI to AD (beta = 0.182, SE = 0.061, p = 0.003) after adjusting for the demographic and clinical variables. This association was replicated in the NACC dataset (beta = 0.094, SE = 0.037, p = 0.009). Further analyses revealed that PRS was associated with the increased ADAS-Cog11/ADAS-Cog13/ADASQ4 scores, tau/ptau levels, and cortical amyloid burdens (PiB-PET and AV45-PET), but decreased hippocampus and entorhinal cortex volumes (p < 0.05). Mediation analysis showed that the effect of PRS on the increased risk of AD may be mediated by Aβ42 (beta = 0.056, SE = 0.026, p = 0.036). CONCLUSION: Our findings suggest that PRS can be useful for the prediction of time to AD and other clinical changes after the diagnosis of MCI.

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Published In

J Alzheimers Dis

DOI

EISSN

1875-8908

Publication Date

2021

Volume

84

Issue

3

Start / End Page

1323 / 1335

Location

Netherlands

Related Subject Headings

  • tau Proteins
  • Positron-Emission Tomography
  • Polymorphism, Single Nucleotide
  • Neuropsychological Tests
  • Neurology & Neurosurgery
  • Male
  • Humans
  • Hippocampus
  • Genome-Wide Association Study
  • Female
 

Citation

APA
Chicago
ICMJE
MLA
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Liu, H., Lutz, M., Luo, S., & Alzheimer’s Disease Neuroimaging Initiative, . (2021). Association Between Polygenic Risk Score and the Progression from Mild Cognitive Impairment to Alzheimer's Disease. J Alzheimers Dis, 84(3), 1323–1335. https://doi.org/10.3233/JAD-210700
Liu, Hongliang, Michael Lutz, Sheng Luo, and Sheng Alzheimer’s Disease Neuroimaging Initiative. “Association Between Polygenic Risk Score and the Progression from Mild Cognitive Impairment to Alzheimer's Disease.J Alzheimers Dis 84, no. 3 (2021): 1323–35. https://doi.org/10.3233/JAD-210700.
Liu H, Lutz M, Luo S, Alzheimer’s Disease Neuroimaging Initiative. Association Between Polygenic Risk Score and the Progression from Mild Cognitive Impairment to Alzheimer's Disease. J Alzheimers Dis. 2021;84(3):1323–35.
Liu, Hongliang, et al. “Association Between Polygenic Risk Score and the Progression from Mild Cognitive Impairment to Alzheimer's Disease.J Alzheimers Dis, vol. 84, no. 3, 2021, pp. 1323–35. Pubmed, doi:10.3233/JAD-210700.
Liu H, Lutz M, Luo S, Alzheimer’s Disease Neuroimaging Initiative. Association Between Polygenic Risk Score and the Progression from Mild Cognitive Impairment to Alzheimer's Disease. J Alzheimers Dis. 2021;84(3):1323–1335.

Published In

J Alzheimers Dis

DOI

EISSN

1875-8908

Publication Date

2021

Volume

84

Issue

3

Start / End Page

1323 / 1335

Location

Netherlands

Related Subject Headings

  • tau Proteins
  • Positron-Emission Tomography
  • Polymorphism, Single Nucleotide
  • Neuropsychological Tests
  • Neurology & Neurosurgery
  • Male
  • Humans
  • Hippocampus
  • Genome-Wide Association Study
  • Female