title: α-Synuclein aggregation in the saliva of familial transthyretin amyloidosis: a potential biomarker.
abstract: Familial transthyretin amyloidosis (ATTR) is an autosomal dominant disease characterized by the formation of transthyretin (TTR) amyloid deposits. This crippling and fatal disease is associated with point mutations in TTR, a protein mainly produced in the liver. Hence, liver transplantation is the only treatment capable of halting disease progression. Ideally, liver transplantation should be performed as early as possible in the disease course before significant neurologic disability has been incurred. Early detection of disease before serious pathological lesions occur is crucial for the clinical management of patients and for morbidity delay. Unfortunately, the presence of TTR mutations by itself is not a predictor of disease onset or progression. In the present work, we observed an increased oligomerization of α-synuclein in the saliva of ATTR symptomatic individuals comparatively to asymptomatic carriers of the same TTR mutation and healthy control subjects. Based on this observation, we propose monitoring α-synuclein oligomers in saliva as a biomarker of ATTR progression. Since α-synuclein plays a major role in several neurodegenerative disorders, assessing its oligomerization state in this fluid provides a non-invasive approach to survey these pathologies.
authors.affiliation: Departamento de Química e Bioquímica, FCUL, Campo Grande, Lisboa, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Guerreiro
authors.forename: Gonçalo
authors.initials: G
authors.lastname: da Costa
authors.forename: Ricardo A
authors.initials: RA
authors.lastname: Gomes
authors.forename: Cristina
authors.initials: C
authors.lastname: Ribeiro-Silva
authors.forename: Samuel
authors.initials: S
authors.lastname: Gilberto
authors.forename: Elia
authors.initials: E
authors.lastname: Mateus
authors.forename: Estela
authors.initials: E
authors.lastname: Monteiro
authors.forename: Eduardo
authors.initials: E
authors.lastname: Barroso
authors.forename: Ana V
authors.initials: AV
authors.lastname: Coelho
authors.forename: Ana
authors.initials: A
authors.lastname: Ponces Freire
authors.forename: Carlos
authors.initials: C
authors.lastname: Cordeiro
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D000682:Amyloid / Q000378:metabolism*; D028226:Amyloidosis, Familial / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D006579:Heterozygote; D006801:Humans; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000302:isolation & purification; D010449:Peptide Mapping; D011228:Prealbumin / Q000378:metabolism*; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D012463:Saliva / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D055815:Young Adult; D051844:alpha-Synuclein / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: D000682:Amyloid; D015415:Biomarkers; D010446:Peptide Fragments; D011228:Prealbumin; D051844:alpha-Synuclein; C076571:transthyretin-related amyloid fibril protein, human