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

Ricardo Apátiga-Pérez, Luis O. Soto-Rojas, B. Berenice Campa-Córdoba, Nabil Itzi Luna-Viramontes, Elvis Cuevas, Ignacio Villanueva-Fierro, Miguel Angel Ontiveros-Torres, Marely Bravo-Muñoz, Paola Flores-Rodríguez, Linda Garcés-Ramirez, Fidel de la Cruz, José Francisco Montiel-Sosa, Mar Pacheco-Herrero, José Luna-Muñoz

Research output: Contribution to journalReview articlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)39-50
Number of pages12
JournalMetabolic brain disease
Issue number1
StatePublished - Jan 2022
Externally publishedYes


  • Alzheimer´s disease
  • Cerebral amyloid angiopathy
  • Neuroinflammation
  • Neurovascular dysfunction
  • Pericyte degeneration

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Neurology
  • Cellular and Molecular Neuroscience


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