Decreased salivary lactoferrin levels are specific to Alzheimer's disease

Marta González-Sánchez; Fernando Bartolome; Desiree Antequera; Veronica Puertas-Martín; Pilar González; Adolfo Gómez-Grande; Sara Llamas-Velasco; Alejandro Herrero-San Martín; David Pérez-Martínez; Alberto Villarejo-Galende; Mercedes Atienza; Miriam Palomar-Bonet; Jose Luis Cantero; George Perry; Gorka Orive; Borja Ibañez; Hector Bueno; Valentin Fuster; Eva Carro

doi:10.1016/j.ebiom.2020.102834

Decreased salivary lactoferrin levels are specific to Alzheimer's disease

Marta González-Sánchez
, Fernando Bartolome
, Desiree Antequera
, Veronica Puertas-Martín
, Pilar González
, Adolfo Gómez-Grande
, Sara Llamas-Velasco
, Alejandro Herrero-San Martín
, David Pérez-Martínez
, Alberto Villarejo-Galende
, Mercedes Atienza
, Miriam Palomar-Bonet
, Jose Luis Cantero
, George Perry
, Gorka Orive
, Borja Ibañez
, Hector Bueno
, Valentin Fuster
, Eva Carro

Research output: Contribution to journal › Article › peer-review

88 Scopus citations

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.

Original language	English
Pages (from-to)	102834
Number of pages	1
Journal	eBioMedicine
Volume	57
DOIs	https://doi.org/10.1016/j.ebiom.2020.102834
State	Published - 1 Jul 2020
Externally published	Yes

Keywords

Alzheimer´s disease
Biomarkers
Frontotemporal dementia
Lactoferrin
Pet imaging
Saliva

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10.1016/j.ebiom.2020.102834

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González-Sánchez, M., Bartolome, F., Antequera, D., Puertas-Martín, V., González, P., Gómez-Grande, A., Llamas-Velasco, S., Herrero-San Martín, A., Pérez-Martínez, D., Villarejo-Galende, A., Atienza, M., Palomar-Bonet, M., Cantero, J. L., Perry, G., Orive, G., Ibañez, B., Bueno, H., Fuster, V., & Carro, E. (2020). Decreased salivary lactoferrin levels are specific to Alzheimer's disease. eBioMedicine, 57, 102834. https://doi.org/10.1016/j.ebiom.2020.102834

@article{d5adc5a857ba401693862a3aab63b052,

title = "Decreased salivary lactoferrin levels are specific to Alzheimer's disease",

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",

author = "Marta Gonz{\'a}lez-S{\'a}nchez and Fernando Bartolome and Desiree Antequera and Veronica Puertas-Mart{\'i}n and Pilar Gonz{\'a}lez and Adolfo G{\'o}mez-Grande and Sara Llamas-Velasco and \{Herrero-San Mart{\'i}n\}, Alejandro and David P{\'e}rez-Mart{\'i}nez and Alberto Villarejo-Galende and Mercedes Atienza and Miriam Palomar-Bonet and Cantero, \{Jose Luis\} and George Perry and Gorka Orive and Borja Iba{\~n}ez and Hector Bueno and Valentin Fuster and Eva Carro",

year = "2020",

month = jul,

day = "1",

doi = "10.1016/j.ebiom.2020.102834",

language = "English",

volume = "57",

pages = "102834",

journal = "eBioMedicine",

issn = "2352-3964",

publisher = "Elsevier B.V.",

}

González-Sánchez, M, Bartolome, F, Antequera, D, Puertas-Martín, V, González, P, Gómez-Grande, A, Llamas-Velasco, S, Herrero-San Martín, A, Pérez-Martínez, D, Villarejo-Galende, A, Atienza, M, Palomar-Bonet, M, Cantero, JL, Perry, G, Orive, G, Ibañez, B, Bueno, H, Fuster, V & Carro, E 2020, 'Decreased salivary lactoferrin levels are specific to Alzheimer's disease', eBioMedicine, vol. 57, pp. 102834. https://doi.org/10.1016/j.ebiom.2020.102834

TY - JOUR

T1 - Decreased salivary lactoferrin levels are specific to Alzheimer's disease

AU - González-Sánchez, Marta

AU - Bartolome, Fernando

AU - Antequera, Desiree

AU - Puertas-Martín, Veronica

AU - González, Pilar

AU - Gómez-Grande, Adolfo

AU - Llamas-Velasco, Sara

AU - Herrero-San Martín, Alejandro

AU - Pérez-Martínez, David

AU - Villarejo-Galende, Alberto

AU - Atienza, Mercedes

AU - Palomar-Bonet, Miriam

AU - Cantero, Jose Luis

AU - Perry, George

AU - Orive, Gorka

AU - Ibañez, Borja

AU - Bueno, Hector

AU - Fuster, Valentin

AU - Carro, Eva

PY - 2020/7/1

Y1 - 2020/7/1

N2 - 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.

AB - 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.

KW - Alzheimer´s disease

KW - Biomarkers

KW - Frontotemporal dementia

KW - Lactoferrin

KW - Pet imaging

KW - Saliva

UR - https://www.scopus.com/pages/publications/85087586823

U2 - 10.1016/j.ebiom.2020.102834

DO - 10.1016/j.ebiom.2020.102834

M3 - Article

C2 - 32586758

AN - SCOPUS:85087586823

SN - 2352-3964

VL - 57

SP - 102834

JO - eBioMedicine

JF - eBioMedicine

ER -

Decreased salivary lactoferrin levels are specific to Alzheimer's disease

Abstract

Keywords

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