RESUMO
We observed atypical astrocytic pTDP-43 pathology in astroglial predominant tauopathy.
Assuntos
Astrócitos/patologia , Demência Frontotemporal/patologia , Degeneração Lobar Frontotemporal/patologia , Tauopatias/patologia , Idoso , Astrócitos/metabolismo , Proteína C9orf72/genética , Proteínas de Ligação a DNA/metabolismo , Feminino , Demência Frontotemporal/metabolismo , Degeneração Lobar Frontotemporal/metabolismo , Humanos , Corpos de Inclusão/patologia , Pessoa de Meia-Idade , Neurônios/patologiaRESUMO
The neuropathological hallmark of the C9orf72 intronic hexanucleotide expansion in frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) is the presence of small ubiquitin/p62-positive and transactive response DNA binding protein 43 kDa (TDP-43)-negative cytoplasmic inclusions in several brain areas. The identification of this histopathological signature is highly predictive of an underlying mutation. In this study, we screened 1800 cases of the Barcelona IDIBAPS Brain Bank, independently of the clinical and final neuropathological diagnosis of the brain donor, for the presence of ubiquitin/p62-positive inclusions in the cerebellum (UPPI). Positive cases were also stained for dipeptide repeats. We identified a total of 21 donors with UPPI and in all of them the C9orf72 hexanucleotide expansion was genetically confirmed. Most donors had an FTLD or to a lesser extent ALS clinico-pathological phenotype. However, 3 cases had been previously classified as having clinically and neuropathologically Lewy body disease. Other co-existing pathologies, especially of the PART-type, were also frequently encountered. This study highlights the importance of the evaluation of ubiquitin/p62-positive cytoplasmic inclusions in all neurodegenerative diseases as a good screening method for the detection of C9orf72 expansion mutation, since this mutation is not rare and can overlap with other neurodegenerative entities.
Assuntos
Proteína C9orf72/metabolismo , Córtex Cerebelar/metabolismo , Mutação/fisiologia , Fenótipo , Agregados Proteicos/fisiologia , Ubiquitina/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína C9orf72/genética , Córtex Cerebelar/patologia , Estudos de Coortes , Feminino , Testes Genéticos/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Ubiquitina/genéticaRESUMO
Los síntomas psicológicos y conductuales asociados a la demencia plantean uno de los retos terapéuticos en el abordaje cotidiano de la enfermedad. Los efectos adversos extrapiramidales y sobre la función cognitiva de los neurolépticos, antipsicóticos clásicos o típicos, desaconsejan su utilización en este campo. A la vista de las publicaciones relacionadas con los nuevos antipsicóticos atípicos (risperidona, olanzapina y quetiapina), se abren nuevas alternativas terapéuticas con un perfil de efectos adversos menor (AU)
