Quantitative pathology and APOE genotype reveal dementia risk and progression in Lewy body disease - PubMed
5 hours ago
- #APOE genotype
- #Lewy body disease
- #Quantitative pathology
- Quantitative pathology using machine learning to measure α-synuclein, amyloid-β, and phosphorylated tau predicts dementia better than conventional staging.
- APOE ε4 genotype dominates overall dementia risk but ε3 carriers develop dementia at lower pathology thresholds.
- Orthostatic hypotension and ischemic pathology increase dementia risk only in ε3 carriers with low proteinopathy.
- Male sex further modulates dementia risk in ε3 carriers with low Lewy and Alzheimer's pathology.
- The SuStaIn algorithm identified four trajectories of Lewy pathology progression, including new patterns with early cortical involvement.
- Co-pathology modeling showed subtypes with early predominance of different proteins and Lewy subtypes propagating in opposite directions.
- Integrating quantitative pathology, genotype, and clinical data reveals distinct pathways to dementia in Lewy body diseases.