Decreased salivary lactoferrin levels are specific to Alzheimer's disease

Background: Evidences of infectious pathogens in Alzheimer's disease (AD) brains may suggest a deteriorated innate immune system in AD pathophysiology. We previously demonstrated reduced salivary lactoferrin (Lf) levels, one of the major antimicrobial proteins, in AD patients. Methods: To assess the clinical utility of salivary Lf for AD diagnosis, we examine the relationship between salivary Lf and cerebral amyloid-beta (A beta) load using amyloid-Positron-Emission Tomography (PET) neuroimaging, in two different cross-sectional cohorts including patients with different neurodegenerative disorders. Findings: The diagnostic performance of salivary Lf in the cohort 1 had an area under the curve [AUC] of 0.95 (0.911-0.992) for the differentiation of the prodromal AD/AD group positive for amyloid-PET (PET+) versus healthy group, and 0.97 (0.924-1) versus the frontotemporal dementia (FTD) group. In the cohort 2, salivary Lf had also an excellent diagnostic performance in the health control group versus prodromal AD comparison: AUC 0.93 (0.876-0.989). Salivary Lf detected prodromal AD and AD dementia distinguishing them from FTD with over 87% sensitivity and 91% specificity. Interpretation: Salivary Lf seems to have a very good diagnostic performance to detect AD. Our findings support the possible utility of salivary Lf as a new non-invasive and cost-effective AD biomarker.This study was supported by Dr. Carro grants from Instituto de Salud Carlos III (FIS15/00780, FIS18/00118), FEDER, Comunidad de Madrid (S2017/BMD-3700; NEUROMETAB-CM), and CIBERNED (PI2016/01). This study was also supported by research grants from the Spanish Ministry of Economy and Competitiveness (SAF201785310-R to Dr. Cantero, PSI2017-85311-P to Dr. Atienza); International Centre on ageing CENIE-POCTEP (0348_CIE_6_E to Dr. Atienza); and CIBERNED (CB06/05/1111 to Dr. Cantero). Dr. Bueno receives research funding from the Instituto de Salud Carlos III, Spain (PIE16/00021, PI17/01799). The H2H-Spain Study was supported in Spain by grant PIE16/00021 from Instituto Carlos III, Ministry of Science, Innovation and Universities, and additional funds from the Centro Nacional de Investigaciones Cardiovasculares (CNIC). The CNIC is supported by the Ministry of Economy, Industry and Competitiveness and the Pro CNIC Foundation, and is a Severo Ochoa Centre of Excellence (SEV-2015-0505). The funders had no role in the conceptualisation, study design, data collection analysis and preparation of this manuscript