RESUMEN
Extracellular amyloid-ß (Aß) plaques and intracellular neurofibrillary tangles constitute the major neuropathological hallmarks of Alzheimer's disease (AD). It is now apparent that parenchymal Aß plaque deposition precedes behavioral signs of disease by several years. The development of agents that can target these plaques may be useful as diagnostic or therapeutic tools. In this study, we synthesized an Aß-targeted lipid conjugate, incorporated it in stealth liposomal nanoparticles and tested their ability to bind amyloid plaque deposits in an AD mouse model. The results show that the particles maintain binding profiles to synthetic Aß aggregates comparable to the free ligand, and selectively bind Aß plaque deposits in brain tissue sections of an AD mouse model (APP/PSEN1 transgenic mice) with high efficiency. When administered intravenously, these long circulating nanoparticles appear to cross the blood-brain barrier and bind to Aß plaque deposits, labeling parenchymal amyloid deposits and vascular amyloid characteristic of cerebral amyloid angiopathy.
Asunto(s)
Enfermedad de Alzheimer/genética , Péptidos beta-Amiloides/administración & dosificación , Precursor de Proteína beta-Amiloide/genética , Presenilina-1/genética , Administración Intravenosa , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Péptidos beta-Amiloides/química , Precursor de Proteína beta-Amiloide/metabolismo , Animales , Barrera Hematoencefálica/metabolismo , Corteza Cerebral/metabolismo , Corteza Cerebral/patología , Modelos Animales de Enfermedad , Hipocampo/metabolismo , Hipocampo/patología , Liposomas/química , Ratones , Ratones Transgénicos , Fosfatidiletanolaminas , Placa Amiloide , Polietilenglicoles , Presenilina-1/metabolismo , Unión ProteicaRESUMEN
A 54 years old male with undiagnosed chronic calcific degenerative aortic valve incompetence presented with acute left anterior chordae tendinae rupture resulting in severe left heart failure and cardiogenic shock. He was successfully treated with emergency double valve replacement using mechanical valves. The pathogenesis of acute rupture of the anterior chordae tendinae, without any evidence of infective endocarditis or ischemic heart disease seems to have been attrition of the subvalvular mitral apparatus by the chronic regurgitant jet of aortic incompetence with chronic volume overload. We review the literature with specific focus on the occurrence of this unusual event.