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Published on: October 20, 2016
Lactoferrin Levels in Cerebrospinal Fluid Exhibit Differential Associations with Alzheimer's Disease
Feiyang Zhao1,2, Raquel Puerta3, Yaxi Wang4
1Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, The University of Texas at San Antonio, San Antonio, TX, USA.
None:
Lactoferrin has been proposed as a minimally invasive biomarker for Alzheimer's disease (AD), but its relationship with established AD pathology remains uncertain. We analyzed paired cerebrospinal fluid (CSF) and plasma SOMAscan proteomic profiles from 1,367 participants in the ACE Alzheimer Center Barcelona cohort, focusing on two lactoferrin-targeting SOMAmers, Seq.14755.4 (LTF1) and Seq.2780.35 (LTF2). LTF1 and LTF2 showed distinct distributions and weak concordance across fluids, indicating that they should not be treated as interchangeable lactoferrin measures. In CSF, LTF2 was associated with lower Aβ42 and AD biomarker-defined status, whereas LTF1 showed subgroup-dependent associations with tau markers that were partly influenced by major CSF proteomic axes and reference-gene adjustment. Neither CSF nor plasma LTF signals predicted conversion from mild cognitive impairment to dementia. GNPC analyses supported the non-interchangeability and compartment specificity of LTF signals and identified a reproducible plasma LTF2-centered network enriched for innate immune and granule biology. These findings suggest that lactoferrin-related signals are assay-, compartment-, and network-context dependent rather than standalone AD biomarkers.
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