Brain-Derived pTau217 and Plasma Proteomic Profiles Across Cognitive and Dementia Groups in Congolese Older Adults

Blood-based biomarkers for Alzheimer disease and related dementias have been validated largely in populations of European ancestry. We characterized plasma proteins in 786 adults aged 65 years or older in Kinshasa, Democratic Republic of the Congo, classified as cognitively unimpaired, mild cognitive impairment, suspected Alzheimer disease, mixed dementia, or vascular dementia. Proteins were quantified with the NULISAseq CNS Disease Panel 120. Sex showed the strongest associations with protein expression, followed by age, whereas APOE ε4 carrier status was associated with four measures. MME was downregulated across all dementia groups and showed the largest effect in each dementia-versus-CU comparison. A random forest model combining 10 biomarkers with age, sex, and APOE ε4 carrier status achieved a mean cross-validated area under the curve of 0.768, compared with 0.612 for brain-derived pTau217 alone. Because biomarker selection and ranking were performed using the full dataset before cross-validation, model performance may be optimistic. These findings support demographic adjustment and population-specific validation of plasma biomarkers and identify MME as a hypothesis-generating signal for further study.