Elevated Flotillin-1 in Saliva and Salivary Glands: A Novel Non-Invasive Biomarker in an Alzheimer’s Disease Mouse Model
Year: 2026
Type: dissertation
Abstract: Background/Objectives: Alzheimer's disease (AD) is currently diagnosed by assessing established biomarkers, including cerebrospinal fluid (CSF) levels of amyloid-β42 (Aβ42), phosphorylated tau, and cerebral amyloid levels by positron emission tomography imaging with Pittsburgh compound B (PiB-PET).Because these methods are invasive or require specialized facilities, less invasive and easily detectable biomarkers are needed.Flotillin-1, a lipid raft-associated protein, is involved in the intracellular trafficking and metabolism of amyloid precursor protein (APP), and has attracted attention as being associated with changes in membrane dynamics accompanying Aβ42 accumulation.Prior reports have shown that lower flotillin-1 levels in the CSF and serum of patients with AD.The present study therefore examined whether salivary flotillin-1, a non-invasive biological specimen, could serve as a biomarker.Methods: Two-and nine-monthold amyloid precursor protein knock-in mice (App NL-G-F ; APP-KI) and wild-type mice (C57BL/6J; WT) were used.Flotillin-1 levels in the saliva and the submandibular glands were measured by Western blotting.In addition, phosphorylated c-Jun N-terminal kinase (p-JNK) and phosphorylated extracellular signal-regulated kinase (p-ERK), members of intracellular signaling pathways involved in the regulation of flotillin-1, were analyzed by Western blotting.Finally, Aβ42 levels in the submandibular glands were analyzed using enzyme-linked immunosorbent assay (ELISA).Results: Flotillin-1 levels in the saliva and the submandibular glands were significantly higher in the 9-month-old APP-KI group than in all other groups, including age-matched WT mice.Further, p-ERK levels were significantly elevated in the 9-month-old APP-KI group, while the submandibular gland Aβ42 levels were markedly increased only in the 9-month-old APP-KI group.Conclusions: Flotillin-1 levels in the saliva and the submandibular glands of APP-KI mice increased in parallel with Aβ42 levels.In addition, the accumulation of Aβ42 in the submandibular glands of APP-KI mice was suggested to be associated with activation of the ERK signaling cascade.These findings indicate that salivary flotillin-1 may serve as a promising non-invasive biomarker for the diagnosis of AD.
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7154871082