Plasma biomarkers of Alzheimer’s disease and related dementia for the prediction of hippocampal atrophy amongst adults in Kinshasa, Democratic Republic of Congo Open Access

Abstract

Objective: Hippocampus is one of the first brain structures affected by Alzheimer’s disease (AD) and its atrophy is a strong indicator of the disease. This study aims to investigate the ability of plasma biomarkers of AD and AD-related dementias amyloid-β (Aβ42/40), phosphorylated tau-181 and 217 (p-tau181, p-tau217), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) to predict hippocampal atrophy in adult individuals in Kinshasa, Democratic Republic of Congo (DRC).

Methods: 85 adult individuals (40 healthy and 45 suspected AD) over 65 years old were evaluated using the Community Screening Instrument for Dementia and Alzheimer’s Questionnaire (AQ). Core AD biomarkers (Aβ42/40, p-tau181, p-tau217), and non-specific AD biomarkers (NfL, GFAP) were measured in blood samples collected at study visit. Hippocampal volumes were measured from study magnetic resonance imaging (MRI). Multiple linear regression was used to evaluate differences in biomarker concentrations by neurological status. Logistic regression models were used to create receiver operating characteristic curves and calculate areas under curve (AUCs) with and without clinical covariates to determine the ability of biomarker concentrations to predict hippocampal atrophy. Plasma biomarkers were used either as single or in combination in the models.

Results:  Reduced Aβ42/40 and elevated p-tau 181 were associated with decreased left hippocampal (LH) volume. Elevated p-tau 181 was similarly associated with total hippocampal (TH) atrophy, with stronger associations for LH than TH volumes. AUC of plasma biomarkers without the clinical covariates individually to discriminate LH, RH, and TH atrophy ranged between 85.1% to 94.3%; 78.0% to 81.8%; and 82.3% to 85.6%, respectively. The AUC of models including clinical covariates and AD biomarkers used in combination to discriminate LH, RH, TH ranged between 83.9%-96.0%; 77.4%-94.9%; and 81.3%-89.0% respectively. Only higher p-tau 181 concentrations were significantly associated with 1.6 to 3.0-fold increased odds of hippocampal atrophy per standard deviation.

 

Conclusion: These results indicate that, consistent with studies in other settings, core AD plasma biomarkers can predict hippocampal atrophy in a population in Sub-Saharan Africa.

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School	Rollins School of Public Health
Department	Executive Masters of Public Health - MPH
Subfield / Discipline	Applied Epidemiology
Degree	M.P.H.
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Pathology Biology, Physiology
Keyword	Democratic Republic of Congo Plasma biomarkers Hippocampus Alzheimer's disease
Committee Chair / Thesis Advisor	Alvaro Alonso, Emory University

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