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. 2017 May 26:8:131-138.
doi: 10.1016/j.dadm.2017.04.002. eCollection 2017.

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

Eva Carro  1   2 , Fernando Bartolomé  1   2 , Félix Bermejo-Pareja  1   3   4 , Alberto Villarejo-Galende  1   3   4 , José Antonio Molina  1   3   4   5 , Pablo Ortiz  6   7 , Miguel Calero  1   8   9 , Alberto Rabano  8 , José Luis Cantero  1   10 , Gorka Orive  11   12
Affiliations

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

Eva Carro et al. Alzheimers Dement (Amst). .

Abstract

Introduction: 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.

Methods: 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.

Results: 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.

Conclusion: This biomarker may offer new insights in the early diagnostics for AD.

Keywords: Alzheimer's disease; Dementia; Diagnosis; Lactoferrin; Mild cognitive impairment; Noninvasive biomarkers; Saliva.

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Figures

Fig. 1
Fig. 1
Salivary lactoferrin levels in patients with aMCI, AD, and healthy controls. (A) Lactoferrin levels decrease in aMCI and AD compared with control group. Boxplot graph shows median, interquartile range, and extreme values of each group. ***P < .001; Kruskal-Wallis test. For lactoferrin expression in pooled saliva samples, see Supplementary Fig. 1. For additional data on lactoferrin levels in PD, see Supplementary Fig. 2. (B) Correlation between saliva levels of lactoferrin and cognitive decline in aMCI and AD groups. Lactoferrin levels appeared to be negatively correlated with severity of the disease (r = −0.742; P < .001; Kendall's tau correlation analysis). (C) Saliva levels of lactoferrin correlated with MMSE score, (r = 0.731; P < .001; Spearman's correlation analysis). (D) Receiver operating characteristic (ROC) curve obtained for the test of saliva lactoferrin levels from the full control group and aMCI/AD group. The area under the ROC curve (AUC), a measure of how well a parameter can distinguish between diagnostic groups, was 1 (95% CI 1–1). The ROC plots represent sensitivity (true positive rate) versus 1 − specificity (false positive rate). Salivary lactoferrin significantly correlates with Aβ42 (E) and total tau (F) in CSF, based on Spearman's correlation analysis. Abbreviations: aMCI, amnestic mild cognitive impairment; AD, Alzheimer's disease; CSF, cerebrospinal fluid; MMSE, Mini–Mental State Examination; PD, Parkinson's disease; T-tau, total tau.
Supplementary Figure 1
Supplementary Figure 1
Supplementary Figure 2
Supplementary Figure 2
Supplementary Figure 3
Supplementary Figure 3
See this image and copyright information in PMC

References

    1. Bateman R.J., Xiong C., Benzinger T.L., Fagan A.M., Goate A., Fox N.C. Clinical and biomarker changes in dominantly inherited Alzheimer's disease. N Engl J Med. 2012;367:795–804. - PMC - PubMed
    1. Blennow K., Zetterberg H. Understanding biomarkers of neurodegeneration: ultrasensitive detection techniques pave the way for mechanistic understanding. Nat Med. 2015;21:217–219. - PubMed
    1. Hulstaert F., Blennow K., Ivanoiu A., Schoonderwaldt H.C., Riemenschneider M., De Deyn P.P. Improved discrimination of AD patients using beta-amyloid(1-42) and tau levels in CSF. Neurology. 1999;52:1555–1562. - PubMed
    1. Small S.A., Perera G.M., DeLaPaz R., Mayeux R., Stern Y. Differential regional dysfunction of the hippocampal formation among elderly with memory decline and Alzheimer's disease. Ann Neurol. 1999;45:466–472. - PubMed
    1. Klunk W.E., Engler H., Nordberg A., Wang Y., Blomqvist G., Holt D.P. Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound-B. Ann Neurol. 2004;55:306–319. - PubMed