biostudies-literatureLiu HNIA NIH HHSCIHR1323-1335https://www.ebi.ac.uk/biostudies/studies/S-EPMC8957404biostudies-literatureUnknown84(3)<h4>Background</h4>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).<h4>Objective</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusion</h4>Our findings suggest that PRS can be useful for the prediction of time to AD and other clinical changes after the diagnosis of MCI.Journal of Alzheimer's disease : JADAssociation Between Polygenic Risk Score and the Progression from Mild Cognitive Impairment to Alzheimer's Disease.PMC8957404P30 AG013846P30 AG028383P30 AG008017P30 AG053760P30 AG010133P50 AG005146R01 AG064803P50 AG005142P50 AG005681P30 AG062715P50 AG047366P50 AG047266P30 AG019610P50 AG023501P30 AG008051P30 AG010129P30 AG013854P30 AG072958P50 AG005138P30 AG062428P50 AG008702P30 AG010124P30 AG012300P50 AG005136P50 AG025688P50 AG047270U01 AG016976P30 AG062421P30 AG035982P30 AG062422P30 AG010161P50 AG005133P30 AG062429P30 AG028716P30 AG049638U01 AG024904P50 AG016573Liu HLutz MLuo SAlzheimer’s Disease Neuroimaging InitiativefalseAssociation Between Polygenic Risk Score and the Progression from Mild Cognitive Impairment to Alzheimer's Disease.<h4>Background</h4>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).<h4>Objective</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusion</h4>Our findings suggest that PRS can be useful for the prediction of time to AD and other clinical changes after the diagnosis of MCI.2021-01-01T00:00:00Z20212026-05-31T19:51:47.974Z2025-04-05T22:19:20.007ZS-EPMC89574043465788510.3233/jad-21070010.3233/JAD-210700