Most studies evaluating neurodegeneration-related proteins include minimal information on image acquisition, correlation coefficients or other objective measures, which are crucial for robust colocalization analysis, as we described recently 14. Furthermore, the synergistic relationship between AD-related pathology and TDP-43 could be suggestive of an interaction between related proteins 13. Indeed, observations in transgenic animal models 11 and colocalization studies on human brain tissue 3, 5, 12 implied an interaction between pTau and α-Syn. It has been suggested that α-Syn induces the formation of tau fibrils and depending on the α-Syn strain, tau and α-Syn synergistically promote the polymerization of each other 9, 10. Furthermore, tau has been reported to colocalize with various other proteins in AD 7, including Aβ, Aβ precursor protein (AβPP), complement factors, phospholipase C, various microtubule-associated proteins, ubiquitin and p62, as well as neurofilaments 8. Depending on the anatomical location (i.e., amygdala or substantia nigra) and disease, hyperphosphorylated-Tau (pTau) has been reported to colocalize to a varying degree with α-Syn and to be present in the same cells with TDP-43 3, 4, 5, 6. In addition, co-existing proteinopathies, where accumulation of more than one type of neurodegeneration-related protein is seen in the same brain, have been frequently observed 1, 2. And finally, TDP-43 in a neuropathological subtype of frontotemporal lobar degeneration (FTLD-TDP) and frequently as limbic TDP-43 proteinopathy associated to AD and other disorders 1. α-Syn is characteristic for Parkinson disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy. tau in primary tauopathies such as progressive supranuclear palsy (PSP), argyrophilic grain disease (AGD), corticobasal degeneration, and, together with Amyloid-β (Aβ), in Alzheimer disease (AD). Each protein accumulates in a characteristic pattern, e.g. The major NDD-proteins include tau, α-synuclein (α-Syn), and TDP-43. These are characterized by loss of neurons and the accumulation of proteins and are therefore termed proteinopathies of the brain 1. Our interest focused on potential protein-protein interactions in various neurodegenerative diseases (NDDs).
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