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. 2021 Sep 6;13(1):150.
doi: 10.1186/s13195-021-00891-8.

Salivary lactoferrin is associated with cortical amyloid-beta load, cortical integrity, and memory in aging

Lucia Reseco  1   2 , Mercedes Atienza  1   2 , Marina Fernandez-Alvarez  1   2 , Eva Carro  2   3 , Jose L Cantero  4   5
Affiliations

Salivary lactoferrin is associated with cortical amyloid-beta load, cortical integrity, and memory in aging

Lucia Reseco et al. Alzheimers Res Ther. .

Abstract

Background: Aging is associated with declining protective immunity and persistent low-grade inflammatory responses, which significantly contribute to Alzheimer's disease (AD) pathogenesis. Detecting aging-related cerebral vulnerability associated with deterioration of the immune system requires from non-invasive biomarkers able to detect failures in the brain-immunity connection. Reduced levels of salivary lactoferrin (sLF), an iron-binding protein with immunomodulatory activity, have been related to AD diagnosis. However, it remains unknown whether decreased sLF is associated with increased cortical amyloid-beta (Aβ) load and/or with loss of cortical integrity in normal aging.

Methods: Seventy-four cognitively normal older adults (51 females) participated in the study. We applied multiple linear regression analyses to assess (i) whether sLF is associated with cortical Aβ load measured by 18F-Florbetaben (FBB)-positron emission tomography (PET), (ii) whether sLF-related variations in cortical thickness and cortical glucose metabolism depend on global Aβ burden, and (iii) whether such sLF-related cortical abnormalities moderate the relationship between sLF and cognition.

Results: sLF was negatively associated with Aβ load in parieto-temporal regions. Moreover, sLF was related to thickening of the middle temporal cortex, increased FDG uptake in the posterior cingulate cortex, and poorer memory. These associations were stronger in individuals showing the highest Aβ burden.

Conclusions: sLF levels are sensitive to variations in cortical Aβ load, structural and metabolic cortical abnormalities, and subclinical memory impairment in asymptomatic older adults. These findings provide support for the use of sLF as a non-invasive biomarker of cerebral vulnerability in the general aging population.

Keywords: Aging; Amyloid-beta PET; Cortical thickness; FDG-PET; Lactoferrin; Saliva.

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Conflict of interest statement

Dr. Carro is co-founder of GEROA Diagnostics.

Figures

Fig. 1
Fig. 1
Effect of age and sex on sLF levels and global Aβ load. A Intra-assay coefficient of variation (CV) of sLF for each participant. B Relationship between salivary total protein content and sLF. C Relationship between age and sLF adjusted by sex. D sLF differences between sexes adjusted by age. E Association of age with global Aβ load (SUVR) adjusted by sex. F Sex differences in cortical Aβ load adjusted by age
Fig. 2
Fig. 2
Association of sLF with cortical Aβ load, cortical thickness and cortical FDG uptake. The t statistics projected into the inflated cortical surfaces indicate the negative associations of sLF with cortical Aβ load (A) after adjustment for age and sex and with cortical thickness (B) and cortical FDG uptake (C) after adjustment for age, sex, and global Aβ load. All cortical measurements were Box-Cox transformed before whole-cortex vertex-wise analysis. Color bar indicates the range of significant t values. Left (L) and right (R)
Fig. 3
Fig. 3
Moderating role of global Aβ load on the association of sLF with cortical thickness or cortical FDG uptake. Whole-cortex vertex-wise assessment of the two-way sLF × global Aβ load interaction on either cortical thickness (A) or cortical FDG uptake (B). The left panel shows the t statistics projected into the inflated cortical surfaces. The right panel shows the scatter plots for the relationship between sLF and the mean of the Box-Cox transformed values of thickness or FDG uptake within the right posterior cingulate cortex in subjects in the lowest and highest tertile of global Aβ load adjusted by age, sex, sLF, and global Aβ load. Color bar indicates the range of significant t values. Right (R)
Fig. 4
Fig. 4
Association of sLF and sLF-related changes in cortical Aβ load with scores in different cognitive domains. A Relationship of sLF with cognition as a function of the cognitive domain. B Association of sLF-related changes in Aβ load over left temporo-parietal (LTP) regions (see Fig. 2A) as a function of the cognitive domain. WM, working memory. SUVR, standardized uptake value ratio
See this image and copyright information in PMC

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