Distinct Phospho-TDP-43 brain distribution in two cases of FTD, one associated with ALS

• Autor(a) principal: Guedes,Álvaro C.B.
• Data de Publicação: 2017
• Outros Autores: Santin,Ricardo, Costa,André S.R., Reiter,Keli C., Hilbig,Arlete, Fernandez,Liana L.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Dementia & Neuropsychologia
• Texto Completo: http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1980-57642017000300249
• topic: TDP-43; frontotemporal dementia; amyotrophic lateral sclerosis; neuropathology

ABSTRACT INTRODUCTION: TDP-43 is an intranuclear protein involved in many cellular processes. When altered, it shows a change in pattern of distribution, as well as in functioning, throughout the Central Nervous System structures. Frontotemporal Lobar Degeneration (FTLD) and Amyotrophic Lateral Sclerosis (ALS) are examples of TDP-43 proteinopathy. These disorders form a clinical spectrum, with some patients having a pure cognitive disorder while others also exhibit motor features. METHODS: We studied two donated brains from patients with a diagnosis of Frontotemporal Dementia (FTD), one of which was associated with ALS (ALS-FTD). After fixation and macroscopic examinations, sample analyses were performed. Specific regions were chosen for the application of immunohistochemistry (IHC) with anti-Aβ, AT8, anti-α-synuclein and anti-phospho-TDP-43. RESULTS: Both brains presented anti-phospho-TDP-43 positivity, but this was not equally distributed throughout the encephalic zones. In the FTD case, the studied brain presented phosphorylated TDP-43- in the frontal cortex, hippocampus, entorhinal cortex and mesencephalon; in the ALS-FTD case, the abnormal protein was also seen in the pons and medulla oblongata. The brain in the ALS-FTD case presented Aβ and AT8 positivity in the hippocampus and entorhinal cortex (Braak I and II). DISCUSSION: The hypothesis supported by scientific literature that these neurodegenerative diseases can have the same etiology with distinct encephalic region involvement is corroborated by the present study.