TY - JOUR
T1 - The neurovascular unit dysfunction in Alzheimer’s disease
AU - Soto-Rojas, Luis O.
AU - Pacheco-Herrero, Mar
AU - Martínez-Gómez, Paola A.
AU - Campa-Córdoba, B. Berenice
AU - Apátiga-Pérez, Ricardo
AU - Villegas-Rojas, Marcos M.
AU - Harrington, Charles R.
AU - de la Cruz, Fidel
AU - Garcés-Ramírez, Linda
AU - Luna-Muñoz, José
N1 - Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/2/2
Y1 - 2021/2/2
N2 - Alzheimer’s disease (AD) is the most common neurodegenerative disease worldwide. Histopathologically, AD presents with two hallmarks: neurofibrillary tangles (NFTs), and aggregates of amyloid β peptide (Aβ) both in the brain parenchyma as neuritic plaques, and around blood vessels as cerebral amyloid angiopathy (CAA). According to the vascular hypothesis of AD, vascular risk factors can result in dysregulation of the neurovascular unit (NVU) and hypoxia. Hypoxia may reduce Aβ clearance from the brain and increase its production, leading to both parenchymal and vascular accumulation of Aβ. An increase in Aβ amplifies neuronal dysfunction, NFT for-mation, and accelerates neurodegeneration, resulting in dementia. In recent decades, therapeutic approaches have attempted to decrease the levels of abnormal Aβ or tau levels in the AD brain. However, several of these approaches have either been associated with an inappropriate immune response triggering inflammation, or have failed to improve cognition. Here, we review the patho-genesis and potential therapeutic targets associated with dysfunction of the NVU in AD.
AB - Alzheimer’s disease (AD) is the most common neurodegenerative disease worldwide. Histopathologically, AD presents with two hallmarks: neurofibrillary tangles (NFTs), and aggregates of amyloid β peptide (Aβ) both in the brain parenchyma as neuritic plaques, and around blood vessels as cerebral amyloid angiopathy (CAA). According to the vascular hypothesis of AD, vascular risk factors can result in dysregulation of the neurovascular unit (NVU) and hypoxia. Hypoxia may reduce Aβ clearance from the brain and increase its production, leading to both parenchymal and vascular accumulation of Aβ. An increase in Aβ amplifies neuronal dysfunction, NFT for-mation, and accelerates neurodegeneration, resulting in dementia. In recent decades, therapeutic approaches have attempted to decrease the levels of abnormal Aβ or tau levels in the AD brain. However, several of these approaches have either been associated with an inappropriate immune response triggering inflammation, or have failed to improve cognition. Here, we review the patho-genesis and potential therapeutic targets associated with dysfunction of the NVU in AD.
KW - Alzheimer’s disease
KW - Amyloid peptide
KW - Astrocytes
KW - Blood-brain barrier
KW - Microglia
KW - Tau protein
UR - http://www.scopus.com/inward/record.url?scp=85101448338&partnerID=8YFLogxK
U2 - 10.3390/ijms22042022
DO - 10.3390/ijms22042022
M3 - Artículo de revisión
C2 - 33670754
AN - SCOPUS:85101448338
SN - 1661-6596
VL - 22
SP - 1
EP - 27
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 4
M1 - 2022
ER -