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APOE ε4 influences the widespread TDP-43 pathological subtype in sporadic amyotrophic lateral sclerosis - PubMed

3 days ago
  • #TDP-43 pathology
  • #ALS
  • #APOE ε4
  • APOE ε4 is linked to a more widespread TDP-43 pathology subtype in sporadic ALS, distinct from motor region-restricted patterns.
  • Study of 145 autopsy-confirmed cases showed APOE ε4 carriers had higher rates of type 2 pathology (widespread cortical involvement).
  • Bayesian structural equation modeling indicated APOE ε4 directly influences TDP-43 subtype, independent of amyloid-β and tau pathology.
  • Rare variants in ALS-associated genes did not significantly affect TDP-43 pathological distribution.
  • Incorporating APOE genotype into ALS stratification could aid in developing subtype-specific therapeutic approaches.