Early diagnosis of mild cognitive impairment and Alzheimer's disease based on salivary lactoferrin

The Alzheimer's disease (AD) process is likely initiated many years before clinical onset. Biomarkers of preclinical disease are critical for the development of disease-modifying or even preventative therapies. Current biomarkers for early disease, including cerebrospinal fluid tau and amyloid β (Aβ) levels, structural and functional magnetic resonance imaging, and the use of brain amyloid imaging, are limited because they are very invasive or expensive. Noninvasive biomarkers may be a more accessible alternative, but none can currently detect preclinical AD with the required sensitivity and specificity. Here, we show a novel, straight-forward, and noninvasive approach for assessment of early stages of cognitive decline. Salivary samples from cases of amnestic mild cognitive impairment (aMCI) and AD, and neurology controls were analyzed. We have discovered and validated a new single saliva biomarker, lactoferrin, which in our cross-sectional investigation perfectly discriminates clinically diagnosed aMCI and AD patients from a cognitively healthy control group. The accuracy for AD diagnosis shown by salivary lactoferrin was greater than that obtained from core cerebrospinal fluid (CSF) biomarkers, including total tau and CSF Aβ42. Furthermore, salivary lactoferrin can be used for population screening and for identifying those underdiagnosed subjects with very early stages of mild cognitive impairment and AD. This biomarker may offer new insights in the early diagnostics for AD. The authors are grateful to Juan Carlos del Castillo who participated in the promotion of this study. The authors specially thank Raquel Cobos, Consuelo Pascual, Desiree Antequera, Jose Javier Aguirre, Belén González-Lahera, Alicia Maroto, and Ana B. Pastor for their helpful support and technical assistance. The authors want to particularly acknowledge the patients enrolled in this study for their participation and the Biobanco imas12 in Hospital 12 de Octubre integrated in the in Spanish Hospital Biobanks Network (RetBioH; www.redbiobancos.es). Biobank is supported by Instituto de Salud Carlos III. This work was supported by a grant from GEROA Diagnostics (grant 2015/82). Sí