PMID- 34406560 OWN - NLM STAT- MEDLINE DCOM- 20220407 LR - 20220407 IS - 1573-7365 (Electronic) IS - 0885-7490 (Linking) VI - 37 IP - 1 DP - 2022 Jan TI - Neurovascular dysfunction and vascular amyloid accumulation as early events in Alzheimer's disease. PG - 39-50 LID - 10.1007/s11011-021-00814-4 [doi] AB - 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 (Abeta) and phosphorylated and truncated tau proteins. Abeta 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 Abeta 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 Abeta 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. CI - (c) 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Apatiga-Perez, Ricardo AU - Apatiga-Perez R AD - National Dementia BioBank. Ciencias Biologicas. Facultad de Estudios Superiores Cuautitlan, Universidad Nacional 13 Autonoma de Mexico, Estado de Mexico, Mexico. AD - Departamento de Fisiologia, Escuela Nacional de Ciencias Biologicas, Instituto Politecnico Nacional, Mexico, Mexico. FAU - Soto-Rojas, Luis O AU - Soto-Rojas LO AD - Facultad de Estudios Superiores Iztacala, Universidad Nacional Autonoma de Mexico, Estado de Mexico, Mexico. FAU - Campa-Cordoba, B Berenice AU - Campa-Cordoba BB AD - National Dementia BioBank. Ciencias Biologicas. Facultad de Estudios Superiores Cuautitlan, Universidad Nacional 13 Autonoma de Mexico, Estado de Mexico, Mexico. AD - Departamento de Fisiologia, Escuela Nacional de Ciencias Biologicas, Instituto Politecnico Nacional, Mexico, Mexico. FAU - Luna-Viramontes, Nabil Itzi AU - Luna-Viramontes NI AD - National Dementia BioBank. Ciencias Biologicas. Facultad de Estudios Superiores Cuautitlan, Universidad Nacional 13 Autonoma de Mexico, Estado de Mexico, Mexico. AD - Departamento de Fisiologia, Escuela Nacional de Ciencias Biologicas, Instituto Politecnico Nacional, Mexico, Mexico. FAU - Cuevas, Elvis AU - Cuevas E AD - Division of Neurotoxicology, National Center for Toxicological Research/U.S. Food and Drug Administration, Jefferson, AR, USA. FAU - Villanueva-Fierro, Ignacio AU - Villanueva-Fierro I AD - CIIDIR, Durango, Instituto Politecnico Nacional, Becario COFAA, Durango, Mexico. FAU - Ontiveros-Torres, Miguel Angel AU - Ontiveros-Torres MA AD - Tecnologico de Monterrey, Escuela de Ingenieria y Ciencias, Toluca, Estado de Mexico, Mexico. FAU - Bravo-Munoz, Marely AU - Bravo-Munoz M AD - Grupo Inmensa, Ciencias neurologicas y salud mental, Chiapas, Mexico. FAU - Flores-Rodriguez, Paola AU - Flores-Rodriguez P AD - CIIDIR, Durango, Instituto Politecnico Nacional, Becario COFAA, Durango, Mexico. FAU - Garces-Ramirez, Linda AU - Garces-Ramirez L AD - Departamento de Fisiologia, Escuela Nacional de Ciencias Biologicas, Instituto Politecnico Nacional, Mexico, Mexico. FAU - de la Cruz, Fidel AU - de la Cruz F AD - Departamento de Fisiologia, Escuela Nacional de Ciencias Biologicas, Instituto Politecnico Nacional, Mexico, Mexico. FAU - Montiel-Sosa, Jose Francisco AU - Montiel-Sosa JF AD - National Dementia BioBank. Ciencias Biologicas. Facultad de Estudios Superiores Cuautitlan, Universidad Nacional 13 Autonoma de Mexico, Estado de Mexico, Mexico. FAU - Pacheco-Herrero, Mar AU - Pacheco-Herrero M AD - Neuroscience Research Laboratory, Faculty of Health Sciences, Pontificia Universidad Catolica Madre y Maestra, Santiago de los Caballeros, Dominican Republic. mpacheco@pucmm.edu.do. FAU - Luna-Munoz, Jose AU - Luna-Munoz J AUID- ORCID: 0000-0002-6927-913X AD - National Dementia BioBank. Ciencias Biologicas. Facultad de Estudios Superiores Cuautitlan, Universidad Nacional 13 Autonoma de Mexico, Estado de Mexico, Mexico. jluna_tau67@comunidad.unam.mx. AD - Banco Nacional de Cerebros-UNPHU, Universidad Nacional Pedro Henriquez Urena, Santo Domingo, Republica Dominicana. jluna_tau67@comunidad.unam.mx. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20210818 PL - United States TA - Metab Brain Dis JT - Metabolic brain disease JID - 8610370 RN - 0 (Amyloid beta-Peptides) SB - IM MH - *Alzheimer Disease/metabolism MH - Amyloid beta-Peptides/metabolism MH - Brain/metabolism MH - *Cerebral Amyloid Angiopathy/metabolism/pathology MH - Humans MH - Plaque, Amyloid/metabolism OTO - NOTNLM OT - Alzheimer s disease OT - Cerebral amyloid angiopathy OT - Neuroinflammation OT - Neurovascular dysfunction OT - Pericyte degeneration EDAT- 2021/08/19 06:00 MHDA- 2022/04/08 06:00 CRDT- 2021/08/18 12:34 PHST- 2021/03/04 00:00 [received] PHST- 2021/07/23 00:00 [accepted] PHST- 2021/08/19 06:00 [pubmed] PHST- 2022/04/08 06:00 [medline] PHST- 2021/08/18 12:34 [entrez] AID - 10.1007/s11011-021-00814-4 [pii] AID - 10.1007/s11011-021-00814-4 [doi] PST - ppublish SO - Metab Brain Dis. 2022 Jan;37(1):39-50. doi: 10.1007/s11011-021-00814-4. Epub 2021 Aug 18.