Genetic subtypes of Alzheimer’s disease are related to differential biomarker and cognitive trajectories

The disease-relevant constellations and disease-specific bicluster structure was apparent in the ADNI MCI sample. Individuals with genetic signatures resembling bicluster 2 exhibited greater decline on the PACC compared to the non-bicluster (p = 0.022) and bicluster 1 groups (p = 0.004). Bicluster 1 demonstrated a somewhat greater increase in florbetapir over time compared to the non-bicluster group, but this difference was not significant (p = 0.129). Bicluster 2 demonstrated a significantly greater increase of CSF p-tau over time compared to the non-bicluster group (p = 0.041) CONCLUSION: These results provide additional evidence for the existence of AD genetic subtypes in an independent dataset. The genetic subtypes exhibit differential pathological accumulation and cognitive decline over time, suggesting that this genetic variation has meaningful consequences for downstream processes and disease manifestation.