Neurovascular dysfunction and vascular amyloid accumulation as early events in Alzheimer's disease

Autor: Paola Flores-Rodríguez, B. Berenice Campa-Córdoba, Marely Bravo-Muñoz, Miguel Ángel Ontiveros-Torres, Mar Pacheco-Herrero, Luis O Soto-Rojas, Linda Garcés-Ramírez, Ricardo Apátiga-Pérez, Nabil Itzi Luna-Viramontes, José Francisco Montiel-Sosa, Ignacio Villanueva-Fierro, José Luna-Muñoz, Elvis Cuevas, Fidel de la Cruz
Rok vydání: 2021
Předmět:
Zdroj: Metabolic Brain Disease. 37:39-50
ISSN: 1573-7365
0885-7490
Popis: Alzheimer's disease (AD) is clinically characterized by a progressive loss of cognitive functions and short-term memory. AD patients present two distinctive neuropathological lesions: neuritic plaques and neurofibrillary tangles (NFTs), constituted of beta-amyloid peptide (Aβ) and phosphorylated and truncated tau proteins. Aβ deposits around cerebral blood vessels (cerebral amyloid angiopathy, CAA) is a major contributor to vascular dysfunction in AD. Vascular amyloid deposits could be early events in AD due to dysfunction in the neurovascular unit (NVU) and the blood-brain barrier (BBB), deterioration of the gliovascular unit, and/or decrease of cerebral blood flow (CBF). These pathological events can lead to decreased Aβ clearance, facilitate a neuroinflammatory environment as well as synaptic dysfunction and, finally, lead to neurodegeneration. Here, we review the histopathological AD hallmarks and discuss the two-hit vascular hypothesis of AD, emphasizing the role of neurovascular dysfunction as an early factor that favors vascular Aβ aggregation and neurodegeneration. Addtionally, we emphasize that pericyte degeneration is a key and early element in AD that can trigger amyloid vascular accumulation and NVU/BBB dysfunction. Further research is required to better understand the early pathophysiological mechanisms associated with NVU alteration and CAA to generate early biomarkers and timely treatments for AD.
Databáze: OpenAIRE
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