Neuropathological comorbidity, genetics and cognition in a Chinese community-based autopsy cohort

Neurodegenerative comorbidities are common and critical, yet data specific to the Chinese population remains limited. In this study, we aimed to investigate the prevalence and associations of neuropathological changes and comorbidities and their correlation with genetics and cognition in a community-dwelling autopsy cohort in China. Datasets of 610 participants were obtained from the National Human Brain Bank for Development and Function at the Chinese Academy of Medical Sciences/Peking Union Medical College. Neuropathological changes analysed included: Alzheimer's disease neuropathological change (ADNC; n = 331); α-synucleinopathies (n = 124), including 120 Lewy body disease (LBD) and 4 multiple system atrophy; limbic-predominant age-related TDP-43 encephalopathy neuropathological changes (LATE-NC; n = 341); primary age-related tauopathy (PART; n = 231); argyrophilic grain disease (n = 107); age-related tau astrogliopathy (n = 144); cerebral amyloid angiopathy (n = 183); and hippocampal sclerosis (n = 46). Frontotemporal lobar degeneration, amyotrophic lateral sclerosis and amygdala-predominant LBD were rare. Descriptive statistics and logistic regression models were used to assess the neuropathological associations. Increased age at death was correlated with increased severity in ADNC, LBD and LATE-NC and with a higher number of comorbidities. APOE ε4 allele frequency in the present autopsy cohort was 13.63%. The presence of the APOE ε4 allele was linked to an advanced ADNC stage and increased comorbidities. The co-pathology prevalence varied by pathologies, with notable increases in specific subgroups: within the ADNC subgroups, LBD, LATE-NC, cerebral amyloid angiopathy and hippocampal sclerosis were more frequent in advanced stages; in the LATE-NC subgroups, ADNC, cerebral amyloid angiopathy and age-related tau astrogliopathy increased, and PART decreased in higher LATE-NC stages. PART cases presented the highest proportion of pure pathology (37.2%) compared with the other groups. Advanced ADNC stages were significantly associated with higher LATE-NC stages, and vice versa. Neocortical LBD was correlated with elevated ADNC levels, and higher LATE-NC stages were associated with worsening LBD pathology. High-level ADNC, neocortical LBD and stage 3 of LATE-NC were identified as independent predictors of severe cognition status. Our study suggests that older age at death and APOE ε4 presence are the risk factors for neuropathological comorbidities in Chinese people. The findings underscore the importance of considering comorbid neurological diagnoses and therapies in clinical practice.