Decreased salivary lactoferrin levels are specific to Alzheimer’s disease

Abstract

Background Efforts focused on developing new less invasive biomarkers for early Alzheimer’s disease (AD) diagnosis are substantial. Evidences of infectious pathogens in AD brains may suggest a deteriorated innate immune system in AD pathophysiology. We previously demonstrated reduced salivary levels of Lf in AD patients, one of the major antimicrobial peptides. 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 in two different cross-sectional cohorts including patients with different neurodegenerative disorders. Study participants for cohort 1 (n = 116) were enrolled from the 12 de Octubre University Hospital Neurology Service in Madrid (Spain) and Pablo de Olavide University in Sevilla (Spain). Study participants for cohort 2 (n = 142) were enrolled as part of the Atherobrain - Heart to Head (H2H) project. Participants underwent neurological and neuropsychological examination, saliva sampling, and amyloid-Positron-Emission Tomography (PET) neuroimaging. Results 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 (95% CI 0.876-0.989). Salivary Lf detected prodromal AD and AD dementia distinguishing them from other dementias as FTD with over 87% sensitivity and 91% specificity. Conclusion Therefore, 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.

Body Fluid Biomarkers for Alzheimer’s Disease—An Up-To-Date Overview

“…An example of such biomarkers is lactoferrin, a globular non-hemic iron-binding glycoprotein that belongs to the family of serum transferrin proteins, and it is mostly synthesized by glandular epithelial cells and neutrophils [ 159 , 160 , 161 , 162 ]. Owing to its iron-binding activity, lactoferrin is a multifunctional protein that exhibits antibacterial, antiviral, antifungal, antioxidant, immunomodulatory, anti-cancer, anti-inflammatory and anti-allergenic properties [ 160 , 162 , 163 , 164 ]. Moreover, while there is evidence of lactoferrin presence within the human brain, its levels are substantially increased in AD patients and those with related neurodegenerative disorders, which could be attributed to its Aβ-binding ability [ 165 , 166 , 167 ].…”

“…Moreover, while there is evidence of lactoferrin presence within the human brain, its levels are substantially increased in AD patients and those with related neurodegenerative disorders, which could be attributed to its Aβ-binding ability [ 165 , 166 , 167 ]. Therefore, lactoferrin has been associated with AD pathogenesis, as it has been detected in the amyloid plaques, NFTs and microglia of AD brains [ 164 , 165 ]. Studies on AD patients are still limited, but there is strong evidence that the salivary levels of lactoferrin significantly decrease when compared to healthy controls and elderly subjects [ 139 , 148 , 164 , 168 ].…”

“…Therefore, lactoferrin has been associated with AD pathogenesis, as it has been detected in the amyloid plaques, NFTs and microglia of AD brains [ 164 , 165 ]. Studies on AD patients are still limited, but there is strong evidence that the salivary levels of lactoferrin significantly decrease when compared to healthy controls and elderly subjects [ 139 , 148 , 164 , 168 ]. Moreover, lactoferrin has also demonstrated its potential for early disease detection, as the accuracy of AD diagnosis using it was greater than with CSF T-tau and Aβ42 [ 139 , 151 ].…”

Relationship between Wine Consumption, Diet and Microbiome Modulation in Alzheimer’s Disease

“…The dissemination of oral microorganisms to the brain is controlled by antimicrobial peptides, as part of the innate immune system. Indeed, in the last decade, several studies have explored the role of these antimicrobial peptides as potential biomarkers for AD; in particular, salivary lactoferrin discriminates between patients with mild cognitive impairment and AD from control subjects [ 119 ]. Another possible way derived from the antimicrobial properties of polyphenols, which can decrease the number of bacteria found in the biofilms of the oral cavity [ 120 , 121 ].…”

Examination of a non-invasive biomarker for the diagnosis of prodromal Alzheimer's disease and Alzheimer's disease Dementia

“…For the first time, González-Sánchez and colleagues examined the potential of Lf as a salivary AD biomarker using participants with known amyloid-Positron-Emission Tomography (PET) status [5] . They were successful in demonstrating that reduced salivary Lf levels correlate with positive amyloid PET results and that reduced Lf levels are specific to AD and mild cognitive impairment (MCI) and not to frontotemporal dementia (FTD) patients.…”