Proteinopathies (proteopathies) are diseases where proteins are abnormally self-associating and aggregating, due to conformational changes. Protein aggregates can be intracellular, extracellular, or both. Proteinopathies can affect any organs, including amyloidosis of the heart, liver, kidneys, and lungs. The most studied proteinopathies are those of the central nervous system (CNS), including Alzheimer’s disease (AD), Parkinson’s disease (PD), and dementia with Lewy bodies (DLB). Proteinopathies of the nervous system affect often both central and peripheral nervous system. Prion diseases, such as Creutzfeldt-Jakob disease (CJD), are infectious proteinopathies.
Most tracers are derivatives of dyes that have been used to stain tissue samples under light microscopy. Congo red and Chrysamine G derivatives bind to fibrillar β-amyloid and tau proteins, both containing stacked β-sheets. Thioflavin T derivatives bind more specifically to fibrillar β-amyloid, but also to myelin.
Bayer TA. Proteinopathies, a core concept for understanding and ultimately treating degenerative disorders? Eur Neuropsychopharmacol. 2015; 25(5): 713-724. doi: 10.1016/j.euroneuro.2013.03.007.
Bischof GN, Endepols H, van Eimeren T, Drzezga A. Tau-imaging in neurodegeneration. Methods 2017; 130: 114-123. doi: 10.1016/j.ymeth.2017.08.003.
Catafau AM, Bullich S. Amyloid PET imaging: applications beyond Alzheimer’s disease. Clin Transl Imaging 2015; 3(1): 39-55. doi: 10.1007/s40336-014-0098-3.
Ezawa N, Katoh N, Oguchi K, Yoshinaga T, Yazaki M, Sekijima Y. Visualization of multiple organ amyloid involvement in systemic amyloidosis using 11C-PiB PET imaging. Eur J Nucl Med Mol Imaging 2018; 45(3): 452-461. doi: 10.1007/s00259-017-3814-1.
Harada R, Okamura N, Furumoto S, Yanai K. Imaging protein misfolding in the brain using β-sheet ligands. Front Neurosci. 2018; 12: 585. doi: 10.3389/fnins.2018.00585.
Law WP, Wang WY, Moore PT, Mollee PN, Ng AC. Cardiac amyloid imaging with 18F-Florbetaben PET: a pilot study. J Nucl Med. 2016; 57(11): 1733-1739. doi: 10.2967/jnumed.115.169870.
Mathis CA, Lopresti BJ, Ikonomovic MD, Klunk WE. Small-molecule PET tracers for imaging proteinopathies. Semin Nucl Med. 2017; 47: 553-575. doi: 10.1053/j.semnuclmed.2017.06.003.
Mayo MC, Bordelon Y. Dementia with Lewy bodies. Semin Neurol. 2014; 34: 182-188. doi: 10.1055/s-0034-1381741.
Takahashi N, Glockner J, Howe BM, Hartman RP, Kawashima A. Taxonomy and imaging manifestations of systemic amyloidosis. Radiol Clin North Am. 2016; 54(3): 597-612. doi: 10.1016/j.rcl.2015.12.012.
Wakabayashi K, Mori F, Tanji K, Orimo S, Takahashi H. Involvement of the peripheral nervous system in synucleopathies, tauopathies and other neurodegenerative diseases of the brain. Acta Neuropathol. 2010; 120(1): 1-12. doi: 10.1007/s00401-010-0706-x.
Updated at: 2018-12-25
Created at: 2017-09-19
Written by: Vesa Oikonen