Proposal of a stepwise approach for CSF biomarkers testing for Alzheimer's Disease in middle‐ and low‐income countries

Abstract Background The incidence and prevalence of dementia are increasing, mainly in low‐ and middle‐income countries. Alzheimer's disease (AD) accounts for the majority of cases. Thus, cost‐effective techniques with lower cost are necessary for scaling up the number of tested individuals in these countries for research and clinical use. Luminex (Millipore xMap®) is a semi‐automated test that can analyze CSF biomarkers with a cost per sample of one fourth of ELISA’s kits. Method We performed a cross‐sectional, case‐control study. After consent, 35 older adults were submitted to clinical and neuropsychological assessment, and then to a lumbar puncture. Based on clinical and neuropsychological assessment, seven patients had a diagnosis of AD’s dementia (McKhann criteria), 17 of amnestic mild cognitive impairment (MCI) (DSM‐5 criteria) and 11 without objective cognitive impairment. CSF biomarkers concentrations were measured by INNOTEST® (ELISA) and Millipore xMap®. Both techniques were compared and the accuracy of the latter was assessed. Result Millipore xMap® measurements showed a robust accuracy for all biomarkers, with AUC of 0.808 for t‐Tau, 0.935 for p‐Tau and 0.952 for Aβ42 compared to ELISA as the reference test. The Aβ42 showed a great sensibility (100%) and the ratio p‐tau/Aβ42 a good specificity (0,944). So, we propose a stepwise approach for the diagnosis of AD based on CSF biomarkers. A patient with a cognitive assessment suggestive of AD (MCI or initial dementia) could be initially assessed for CSF biomarkers with a more affordable test, such as Luminex. If there is a need of a confirmation due low pretest probability or the need of a more specific test for a high‐cost treatment, researchers and clinicians could order an ELISA test in the same CSF sample or additional molecular neuroimaging techniques. For patients with a high pretest probability, Luminex has excellent accuracy and can define biological diagnosis. Conclusion The use of Millipore xMap® as the first step in a stepwise approach for the assessment of suspected AD in middle‐ and low‐income countries cases is promising, considering its accuracy and lower cost per sample. Still, the implementation of the proposed approach in this study should be replicated in larger and different samples.