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 Proteica