Biomarkers

Area of Science:

• Neuroscience
• Genetics
• Medical Imaging

Background:

• Sporadic Alzheimer's disease (AD) comprises over 90% of cases, with genetic factors playing a significant role.
• Investigating polygenic risk scores (PRS) offers insights into gene-gene interactions influencing AD-related brain changes.
• Understanding genetic contributions to AD is crucial for developing effective diagnostic and therapeutic strategies.

Purpose of the Study:

• To examine the association between polygenic risk scores (PRS) for Alzheimer's disease (AD) and regional grey matter volume.
• To explore how PRS, incorporating or excluding APOE, relates to brain structure in different participant groups.
• To determine the potential of PRS as a biomarker for AD diagnosis.

Main Methods:

• Utilized data from 738 participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI).
• Constructed two sets of PRS (PRSwithAPOE and PRSwithoutAPOE) using three different single nucleotide polymorphism (SNP) thresholds.
• Processed T1-weighted MRI scans to extract volumes of 114 brain regions of interest using SPM12.

Main Results:

• PRS including APOE (PRSwithAPOE) correlated with bilateral hippocampal and amygdala volumes across all participants.
• Stratified analyses revealed PRSwithAPOE associations with specific regional volumes in cognitively unimpaired, MCI, and AD groups.
• Amyloid-positive individuals showed PRSwithAPOE associations with hippocampal, amygdala, and middle occipital gyrus volumes.

Conclusions:

• Polygenic risk scores for AD are associated with regional grey matter volumes characteristic of the disease.
• The inclusion of APOE SNPs significantly influences the observed associations between PRS and brain structure.
• PRS, particularly PRSwithAPOE, may serve as a valuable tool for differentiating AD patients from those with mild cognitive impairment or normal cognition.