Fig. 1

Adjusted prevalence of neuropathological changes across age at death stratified by APOE ε4 status. A–F illustrate the adjusted prevalence of various Alzheimer’s disease related neuropathological markers and other major neurodegenerative pathologies across age at death. Red lines indicate those without the APOE ε4 allele (APOE ε4 negative) while blue lines represent individuals with APOE ε4 positivity. The adjusted prevalence was derived from modified Poisson regression models adjusted for education level and sex and included the interaction term between APOE ε4 and age at death, with robust standard errors applied to account for heteroscedasticity. The line represents the mean adjusted prevalence, and the surrounding band denote 95% confidence intervals calculated from robust standard errors. A: Prevalence of neuritic plaques based on the CERAD score (none versus sparse, intermediate, and frequent). B: Prevalence of Braak staging (none versus low (B1), intermediate (B2), and high (B3)). C: Prevalence of diffuse neuritic plaques based on the CERAD semiquantitative score (none, sparse, intermediate, and frequent). D: Prevalence of Lewy body disease (LBD) pathology (none versus brainstem predominant, limbic or amygdala-predominant, and neocortical). E: Prevalence of TDP-43 proteinopathy in any region. E: Prevalence of hippocampal sclerosis presence. The hash symbol (#APOE x Age at Death) indicates significant interactions between APOE ε4 positivity and age at death. Abbreviations: CI confidence interval; APOE ε4 Apolipoprotein E epsilon 4 allele; CERAD Consortium to Establish a Registry for Alzheimer’s Disease; Braak staging classification of neurofibrillary tangle severity; LBD Lewy body disease; TDP-43 transactive response DNA binding protein 43