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.

Keywords::

• Familial transthyretin amyloidosis
• saliva
• systemic amyloidosis
• transthyretin
• α-synuclein

Acknowledgments

The authors wish to acknowledge Nurse Margarida for her outstanding cooperation in this work.

Declaration of Interest: Work funded by the Fundação para a Ciência e a Tecnologia do Ministério da Ciência Tecnologia e Ensino Superior, Portugal, for the Intrument Network Grant [REDE/1501/REM/2005], for grants [PDTC/QUI/70610/2006] and [SFRH/BPD/41037/2007] and Centro de Química e Bioquímica plurianual funding [QUI-LVT-612].