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Acta Neuropathol (2013) 125:463465 DOI 10.1007/s00401-013-1089-6
CORRESPONDENCE
Inclusions in frontotemporal lobar degeneration with TDP-43 proteinopathy (FTLD-TDP) and amyotrophic lateral sclerosis (ALS), but not FTLD with FUS proteinopathy (FTLD-FUS), have properties of amyloid
Eileen H. Bigio Jane Y. Wu Han-Xiang Deng Esther N. Bit-Ivan
Qinwen Mao Rakhee Ganti Melanie Peterson Nailah Siddique
Changiz Geula Teepu Siddique Marsel Mesulam
Received: 14 January 2013 / Accepted: 23 January 2013 / Published online: 3 February 2013 Springer-Verlag Berlin Heidelberg 2013
TDP-43 and FUS normal cytoplasmic functions are thought to involve regulated aggregation and disaggregation [1, 5, 8], similar to that of prion proteins, where aggregation occurs by a self-templating process, likely involving properties of amyloid, or beta-pleated sheet structure. Both thioavin-T and thioavin-S uoresce when bound to amyloid brils [7]. We previously showed that TDP-43 peptides form amyloidogenic brils, binding to thioavin-T [3]. Recently, TDP-43-positive lower motor neuron (LMN) inclusions in 28 % of 47 cases of ALS, but no inclusions in 22 FTLD-TDP cases, were shown to be positive with thioavin-S [6]. Using thioavin-S, we surveyed brain tissues from 44 cases, including FTLD-TDP
type A (17 cases), type B (14 cases), type C (3 cases), sporadic ALS (2 cases), familial ALS (FALS) (2 each with SOD1 and C9orf72 mutations), and FTLD-FUS, including atypical FTLD-U (aFTLD-U, 2 cases) and basophilic inclusion body disease (BIBD, 2 cases). Our routine modied thioavin-S stain includes pretreatment of tissue sections with potassium permanganate and bleaching with potassium metabisulte and oxalic acid followed by treatment with sodium hydroxide and hydrogen peroxide, removing lipid autouorescence and resulting in improved denition of pathological lesions. Slides were viewed using a Nikon BV-2A lter cube. Confocal microscopy was performed using thioavin-S staining as above and phospho TDP43 (pS409/410-1). Inclusions in most cases of FTLDTDP and ALS were thioavin-S positive. The density and distribution of thioavin-S positive inclusions was similar to that seen with ubiquitin and fewer than with TDP-43 immunohistochemistry. In FTLD-TDP type...