A/T/N polygenic risk score for cognitive decline in old age

Abstract:

INTRODUCTION We developed a novel polygenic risk score (PRS) based on the A/T/N (amyloid plaques (A), phosphorylated tau tangles (T), and neurodegeneration (N)) framework and compared a PRS based on clinical AD diagnosis to assess which was a better pbkp_redictor of cognitive decline. METHODS We used summary statistics from genome wide association studies of cerebrospinal fluid amyloid-β (Aβ42) and phosphorylated-tau (ptau181), left hippocampal volume (LHIPV), and late-onset AD dementia to calculate PRS for 1181 participants in the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Individual PRS were averaged to generate a composite A/T/N PRS. We assessed the association of PRS with baseline and longitudinal cognitive composites of executive function and memory. RESULTS The A/T/N PRS showed superior pbkp_redictive performance on AD biomarkers and executive function decline compared to the clinical AD PRS. DISCUSSION Results suggest that integration of genetic risk across AD biomarkers may improve pbkp_rediction of disease progression. Research in Context Systematic Review Authors reviewed relevant literature using PubMed and Google Scholar. Key studies that generated and validated polygenic risk scores (PRS) for clinical and pathologic AD were cited. PRS scores have been increasingly used in the literature but clinical utility continues to be questioned. Interpretation In the current research landscape concerning PRS clinical utility in the AD space, there is room for model improvement and our hypothesis was that a PRS with integrated risk for AD biomarkers could yield a better model for cognitive decline …

Año de publicación:

2019

Keywords:

Fuente:

google