Association of LATE-NC with advanced neuropathological lesions: a population-based autopsy study

Background: Limbic-predominant age-related TDP-43 encephalopathy neuropathological change (LATE-NC) is characterized by amnestic dementia and often coexists with other neuropathological lesions. We aimed to investigate the frequency of other neuropathological lesions and their associations with LATE-NC. Method: This cross-sectional study analyzed a population-based sample of 1,434 Brazilians from the Biobank for Aging Studies at the University of São Paulo Medical School. Neuropathological data were collected for Braak for Parkinson's Disease (PD), Braak for neurofibrillary tangles (NFT), amyloid-β burden (CERAD), LATE-NC, lacunar infarcts, cerebral amyloid angiopathy, and hyaline arteriolosclerosis. Ordinal logistic regression evaluated the relationship between LATE-NC and the staging of other neuropathological lesions. For descriptive analyses, LATE-NC was dichotomized into binary categories: absent (stages 0–1) and present (stages 2–3). Models were adjusted for sociodemographic factors, clinical variables, and neuropathological lesions. In each analysis, the outcome lesion was excluded from the adjustments. Result: Sociodemographic and clinical variables varied significantly across participants at different LATE-NC stages. Participants in LATE-NC stages 1 and 2 exhibited a higher frequency of advanced neuropathological changes compared to those without LATE-NC, while participants in stage 3 showed lower frequencies. Dichotomized LATE-NC demonstrated an overall higher frequency of all neuropathological lesions associated with LATE-NC. Adjusted analyses for sociodemographic and clinical factors along with other neuropathological lesions, demonstrated a significant association only between LATE-NC presence and advanced Braak PD stages (OR=1.46, 95%CI 1.09–1.94, p=0.008). Conclusion: Higher LATE-NC stages were correlated with more neuropathological lesions, but only Braak PD remained independently associated after adjustments.