Abstract
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.
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References
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Funding
This work was supported by Fondo Nacional de Ciencia, Tecnologia, FONDOCyT, from the Ministry of Higher Education, Science and Technology, Dominican Republic (2015-3A2-127 to MP-H and 2018-2019-2A3-208 to JLM and MP-H).
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M.P–H, J.L-M and L.O.S-R contributed to the conceptualization, writing, review and editing of the manuscript. R.A-P, B.B.C–C and N.I.L-V contributed to the writing, review and editing of the manuscript. E.C, I.V-F, M.A.O-T, M.B-M, P.F-R, L.G-R, FC, J.F.M-S contributed to the review of the manuscript. All authors have read and agreed to the published version of the manuscript.
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Apátiga-Pérez, R., Soto-Rojas, L.O., Campa-Córdoba, B.B. et al. Neurovascular dysfunction and vascular amyloid accumulation as early events in Alzheimer's disease. Metab Brain Dis 37, 39–50 (2022). https://doi.org/10.1007/s11011-021-00814-4
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DOI: https://doi.org/10.1007/s11011-021-00814-4