Proteinopathies

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, kidney, 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.

PET tracers have been developed for studying the three main types of aggregated amyloid proteins: β-amyloid, tau proteins, and α-synuclein.

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.


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References:

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Catafau AM, Bullich S. Amyloid PET imaging: applications beyond Alzheimer’s disease. Clin Transl Imaging 2015; 3(1): 39-55.

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 2017; (in press).

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.

Mathis CA, Lopresti BJ, Ikonomovic MD, Klunk WE. Small-molecule PET tracers for imaging proteinopathies. Semin Nucl Med. 2017; 47: 553-575.

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.

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.



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Created at: 2017-09-19
Updated at: 2017-12-13
Written by: Vesa Oikonen