Decreased Release of the Angiogenic Peptide Vascular Endothelial Growth Factor in Alzheimer’s Disease: Recovering Effect with Insulin and DHEA Sulfate

Changes of vascular endothelial growth factor (VEGF) secretion have recently been demonstrated in patients with Alzheimer’s disease (AD). Since VEGF has been involved in brain angiogenesis, neuroprotection and cerebromicrovascular exchange of substrates and nutrients, the study of VEGF could have im...

Full description

Saved in:
Bibliographic Details
Published in:Dementia and geriatric cognitive disorders 2005-01, Vol.19 (1), p.1-10
Main Authors: Solerte, Sebastiano Bruno, Ferrari, Ettore, Cuzzoni, Gianni, Locatelli, Eleonora, Giustina, Andrea, Zamboni, Mauro, Schifino, Nicola, Rondanelli, Mariangela, Gazzaruso, Carmine, Fioravanti, Marisa
Format: Article
Language:English
Subjects:
Adult
Age Factors
Aged
Alzheimer Disease - immunology
Amyloid beta-Peptides - pharmacology
Angiogenic Proteins - metabolism
Biological and medical sciences
Brain - blood supply
Cells, Cultured
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
Dehydroepiandrosterone - pharmacology
Dementia, Vascular - immunology
Dose-Response Relationship, Drug
Female
Humans
Insulin - pharmacology
Killer Cells, Natural - drug effects
Killer Cells, Natural - immunology
Male
Medical sciences
Microcirculation - drug effects
Middle Aged
Neurology
Neuropharmacology
Neuroprotective agent
Original Research Article
Peptide Fragments - pharmacology
Pharmacology. Drug treatments
Reference Values
Vascular diseases and vascular malformations of the nervous system
Vascular Endothelial Growth Factor A - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Changes of vascular endothelial growth factor (VEGF) secretion have recently been demonstrated in patients with Alzheimer’s disease (AD). Since VEGF has been involved in brain angiogenesis, neuroprotection and cerebromicrovascular exchange of substrates and nutrients, the study of VEGF could have important relapses into the pathogenesis and treatment of AD. Within this context, 35 healthy subjects (16 of young and 19 of old age), 18 patients with dementia of the vascular type (VAD) and 22 with dementia of the Alzheimer’s type (AD) were included in the study. VEGF levels were determined in the supernates of circulating natural killer (NK) immune cells isolated by immunomagnetic separation (pure CD16 + CD56 + NK cells at a final density of 7.75 × 10 6 cells/ml). VEGF was measured in spontaneous conditions (without modulation) and after exposure of NK cells with IL-2, lipopolysaccharide (LPS), dehydroepiandrosterone sulfate (DHEAS), LPS + insulin, amyloid-β (Aβ) fragment 1–42, the inactive sequence Aβ 40–1 and Aβ 1–42 + insulin. A significant decrease in VEGF released by NK cells was demonstrated in AD subjects compared to the other groups. No differences of VEGF levels were found between healthy subjects of old age and the VAD group. The incubation with LPS and DHEAS significantly increased, in a dose-dependent manner, VEGF levels in AD as well as in healthy subjects of young and old age and in VAD patients. The incubation of NK cells with Aβ 1–42 completely suppressed VEGF generation in AD subjects, also reducing VEGF release in the other groups. The co-incubation of NK with LPS + insulin, at different molar concentrations, significantly restored (4- and 6-fold increase from LPS alone) VEGF in AD, also enhancing VEGF secretion in healthy subjects and the VAD group, while the co-incubation of NK with Aβ 1–42 + insulin promptly abolished the negative effects of Aβ 1–42 on VEGF release. These data might suggest that the decreased VEGF secretion by peripheral immune cells of AD subjects could have a negative role for brain angiogenesis, neuroprotection and for brain microvascular permeability to nutrients, increasing brain frailty towards hypoxic injuries. On the contrary, insulin and DHEAS could have beneficial effects in AD, as well as in VAD and in physiological aging, by increasing, in a dose-dependent fashion, VEGF availability by peripheral and resident immune and endothelial cells, so contributing to increase its circulating pool.
ISSN:1420-8008
1421-9824
DOI:10.1159/000080963