RESUMEN

Alzheimer's disease is a complex disease characterized by overlapping phenotypes with different neurodegenerative disorders. Oligomers are considered the most toxic species in amyloid pathologies. We examined human AD brain samples using an anti-oligomer antibody generated in our laboratory and detected potential hybrid oligomers composed of amyloid-ß, prion protein, α-synuclein, and TDP-43 phosphorylated at serines 409 and 410. These data and in vitro results suggest that Aß oligomer seeds act as a template for the aggregation of other proteins and generate an overlapping phenotype with other neuronal disorders. Furthermore, these results could explain why anti-amyloid-ß therapy has been unsuccessful.

Asunto(s)

Enfermedad de Alzheimer/complicaciones , Enfermedad de Alzheimer/patología , Péptidos beta-Amiloides/metabolismo , Angiopatía Amiloide Cerebral/etiología , Proteínas de Unión al ADN/metabolismo , Lóbulo Frontal/metabolismo , Fragmentos de Péptidos/metabolismo , Anciano , Anciano de 80 o más Años , Animales , Línea Celular Tumoral , Femenino , Lóbulo Frontal/patología , Humanos , Imagenología Tridimensional , Masculino , Ratones , Neuroblastoma/patología , Neuroimagen , Priones/metabolismo , alfa-Sinucleína/metabolismo