Decreased salivary lactoferrin levels are specific to Alzheimer's disease

EBioMedicine. 2020 Jul:57:102834. doi: 10.1016/j.ebiom.2020.102834. Epub 2020 Jun 22.

Abstract

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-β (Aβ) 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.

Funding: Instituto de Salud Carlos III (FIS15/00780, FIS18/00118), FEDER, Comunidad de Madrid (S2017/BMD-3700; NEUROMETAB-CM), and CIBERNED (PI2016/01) to E.C.; Spanish Ministry of Economy and Competitiveness (SAF2017-85310-R) to J.L.C., and (PSI2017-85311-P) to M.A.; International Centre on ageing CENIE-POCTEP (0348_CIE_6_E) to M.A.; Instituto de Salud Carlos III (PIE16/00021, PI17/01799), to H.B.

Keywords: Alzheimer´s disease; Biomarkers; Frontotemporal dementia; Lactoferrin; Pet imaging; Saliva.

MeSH terms

  • Aged
  • Alzheimer Disease / diagnosis*
  • Alzheimer Disease / diagnostic imaging
  • Alzheimer Disease / genetics
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / genetics
  • Amyloid beta-Peptides / metabolism
  • Biomarkers / metabolism
  • Brain / diagnostic imaging
  • Brain / metabolism
  • Cognitive Dysfunction / genetics*
  • Cognitive Dysfunction / pathology
  • Female
  • Humans
  • Immunity, Innate / genetics
  • Lactoferrin / genetics*
  • Lactoferrin / metabolism
  • Male
  • Middle Aged
  • Neuroimaging / methods
  • Positron-Emission Tomography / methods
  • Salivary Glands / metabolism*
  • Tomography, X-Ray Computed
  • tau Proteins / genetics

Substances

  • Amyloid beta-Peptides
  • Biomarkers
  • tau Proteins
  • Lactoferrin