Non-productive angiogenesis disassembles Aß plaque-associated blood vessels

• DOI: 10.1038/s41467-021-23337-z
• Publication Date: 2021-05-25T10:02:59Z
• Authors: Maria I. Alvarez-...; Alicia E. Rosales...; Rosana March-Diaz; Guiomar Rodriguez...; Nieves Lara-Ureña; Clara Ortega-de S...; Manuel A. Sanchez...; Miguel Martin-Bornez; Pedro Gómez-Gálvez; Pablo Vicente-Mun...; Beatriz Fernandez...; Miguel A. Marchena; Andrea S. Bullone...; Jose C. Davila; Rocio Gonzalez-Ma...; Jose L. Trillo-Co...; Ana C. Sanchez-Hi...; Raquel del Toro; Francisco G. Scholl; Eloisa Herrera; Martin Trepel; Jakob Körbelin; Luis M. Escudero; Javier Villadiego; Miriam Echevarria; Fernando de Castro; Antonia Gutierrez; Alberto Rabano; Javier Vitorica; Alberto Pascual
• Keywords: Malformaciones vasculares; Endothelial cells; Plaque, Amyloid; INHIBITS TUMOR-GROWTH; Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans; Medical Subject Headings::Anatomy::Cardiovascular System::Blood Vessels::Microvessels; Mice; Blood vessels; Péptidos beta-amiloides; Enfermedad de Alzheimer; Medical Subject Headings::Diseases::Nervous System Diseases::Neurodegenerative Diseases::Tauopathies::Alzheimer Disease; Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Gene Expression Profiling; BRAIN; Mice, Knockout; Medical Subject Headings::Anatomy::Cardiovascular System::Blood Vessels; ddc:610; 0303 health sciences; SENILE PLAQUES; Péptidos beta-Amiloides; Neovascularization, Pathologic; Reverse Transcriptase Polymerase Chain Reaction; Placa amiloide; Q; Presenilins; Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice::Mice, Transgenic; Brain; HEPARAN-SULFATE PROTEOGLYCAN; VEGF; Multidisciplinary Sciences; ALZHEIMERS-DISEASE; Medical Subject Headings::Organisms::Eukaryota::Animals; Vasos sanguíneos; Encéfalo; Science & Technology - Other Topics; Medical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathological Conditions, Anatomical::Plaque, Amyloid; Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Amyloid beta-Peptides; Female; Alzheimer disease; Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice::Mice, Mutant Strains::Mice, Knockout; EXPRESSION; Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Presenilins; Medical Subject Headings::Anatomy::Cells::Epithelial Cells::Endothelial Cells; AMYLOID PLAQUES; Vascular malformations; Presenilinas; Science; Mice, Transgenic; Medical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain; Article; MICROGLIA; Plaque, amyloid; 03 medical and health sciences; Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Nucleic Acid Amplification Techniques::Polymerase Chain Reaction::Reverse Transcriptase Polymerase Chain Reaction; Alzheimer Disease; Animals; Humans; Science & Technology; Amyloid beta-Peptides; Gene Expression Profiling; Medical Subject Headings::Diseases::Animal Diseases::Disease Models, Animal; Células endoteliales; Endothelial Cells; Medical Subject Headings::Check Tags::Female; Medical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Metaplasia::Neovascularization, Pathologic; Mice, Inbred C57BL; Disease Models, Animal; ENDOTHELIAL GROWTH-FACTOR; Microvessels; Skin Abnormalities; Medical Subject Headings::Diseases::Skin and Connective Tissue Diseases::Skin Diseases::Skin Abnormalities; Blood Vessels; Angiogenesis; Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice::Mice, Inbred Strains::Mice, Inbred C57BL

Abstract The human Alzheimer’s disease (AD) brain accumulates angiogenic markers but paradoxically, the cerebral microvasculature is reduced around Aß plaques. Here we demonstrate that angiogenesis started near plaques in both AD mouse models and samples. However, endothelial cells express molecular signature of non-productive (NPA) accumulate, plaques, a tip cell marker IB4 reactive vascular anomalies with NOTCH activity. Notably, NPA induction by loss presenilin, whose mutations cause familial which activity has been shown to decrease age, produced similar phenotype absence pathology. We also show plaque-associated locally disassembles blood vessels, leaving behind scars, microglial phagocytosis contributes local cells. These results define role microglia vessel disassembly highlight component presenilin function AD.