Diagnostic performance of Alzheimer’s disease blood biomarkers in a Brazilian cohort

Abstract Background Blood-based biomarkers (BBMs) have emerged as promising tools to enhance Alzheimer’s disease (AD) diagnosis. Despite two-thirds of dementia cases occurring in the Global South, research on BBMs has predominantly focused on populations from the Global North. This geographical disparity hinders our understanding of BBM performance in diverse populations. To address this, we evaluated the diagnostic properties of AD BBMs in a real-world memory clinic from Brazil, one of the largest countries in the Global South. We measured blood and cerebrospinal fluid (CSF) biomarkers - amyloid-β (Aβ)40, Aβ42, phosphorylated tau (p-tau) 217, neurofilament light (NfL) chain, and glial fibrillary acidic protein (GFAP) - in 59 individuals. Sample comprised 20 cognitively unimpaired (CU) individuals, 22 with AD dementia, and 17 with vascular dementia (VaD). We compared BBM levels across diagnostic groups and assessed their discriminative ability for AD. Notably, individuals with VaD and AD had lower educational levels (6.8±3.0) compared to CU individuals (61.4±6.6). Among the BBMs tested, plasma p-tau217 demonstrated the best performance, exhibiting high accuracy in differentiating CU from AD (AUC 0.96) and Aβ pathology (AUC 0.98). However, the ability of AD BBMs to distinguish between AD and VaD was lower than expected (AUC from 0.52 to 0.79), particularly when compared to studies from the Global North. Our findings highlight the potential utility of BBMs for AD diagnosis in real-world settings within the Global South. However, they also underscore the need for proper implementation and validation of these biomarkers within these populations to ensure accurate and reliable results. Competing Interest Statement WVB has served in the scientific advisory board of masima, and he is also a co-founder and a minority shareholder at masima. ERZ has served in the scientific advisory board of Nintx, Novo Nordisk and masima. He is also a co-founder and a minority shareholder at masima. Funding Statement This project was partly funded by FIPE/HCPA. WVB receives financial support by the Alzheimer's Association (AACSFD-22-928689). PCLF is supported by the Alzheimer's Association (AARFD-22-923814). BB is supported by the Alzheimer's Association (grant No. AARFD-22-974627) and the National Institute of Aging (5 P01 AG025204-17). CSA is supported by the Global Brain Health Institute, Alzheimer's Association, and Alzheimer's Society (grant No. GBHI ALZ UK-23-971089), and Alzheimer's Association (grant No. 24AACSF-1200375). DG is supported by the Alzheimer's Association (AARFD-22-928702). GP is supported by the Alzheimer's Association (24AARFD-1243899). PRN is supported by the Fonds de Recherche du Quebec Sante (FRQS; Chercheur Boursier, 2020-VICO-279314) and Colin J. Adair Charitable Foundation. TAP is supported by the NIA (5R01AG075336, 5R01AG073267). ERZ receives financial support from CNPq [312410/2018-2; 435642/2018- 9; 312306/2021-0; 409066/2022-2], ARD/FAPERGS [21/2551-0000673-0], Alzheimer's Association [AARGD-21- 850670], CNPQ/FAPERGS/PRONEX [16/2551-0000475-7], the Brazilian National Institute of Science and Technology in Excitotoxicity and Neuroprotection [465671/2014-4], Instituto Serrapilheira [Serra-1912-31365], and Alzheimer's Association and National Academy of Neuropsychology [ALZ-NAN-22-928381]. Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee/5.844.578 of the Hospital de Clinicas de Porto Alegre approved this study gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability All data produced in the present study are available upon reasonable request to the authors