β amyloid angiogenic activity in vitro and in vivo

Boscolo, Elisa; Folin, Marcella; Nico, Beatrice; Grandi, Claudio; Mangieri, Domenica; Longo, Vito; Scienza, Renato; Zampieri, Paolo; Conconi, Maria Teresa; Parnigotto, Pier Paolo; Ribatti, Doménico

doi:10.3892/ijmm.19.4.581

Cited by 33 publications

(39 citation statements)

References 18 publications

(22 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…An unresolved issue is whether AD pathways induce detrimental effects on CV length and the significance for cognitive dysfunction. There is evidence of both higher [7, 9, 13] and lower [18, 25, 29, 39] vessel length and/or density (vessel coverage) in AD-patients and mice (AD-Tg) that overproduce an important contributor to AD progression; human amyloid-beta (Aβ). Angiogenic growth factors (AGFs) are key for controlling total vessel coverage.…”

Section: Introductionmentioning

confidence: 99%

Epidermal growth factor prevents APOE4 and amyloid-beta-induced cognitive and cerebrovascular deficits in female mice

Thomas

Zuchowska

Morris

et al. 2016

acta neuropathol commun

104

View full text Add to dashboard Cite

Cerebrovascular (CV) dysfunction is emerging as a critical component of Alzheimer’s disease (AD), including altered CV coverage. Angiogenic growth factors (AGFs) are key for controlling CV coverage, especially during disease pathology. Therefore, evaluating the effects of AGFs in vivo can provide important information on the role of CV coverage in AD. We recently demonstrated that epidermal growth factor (EGF) prevents amyloid-beta (Aβ)-induced damage to brain endothelial cells in vitro. Here, our goal was to assess the protective effects of EGF on cognition, CV coverage and Aβ levels using an AD-Tg model that incorporates CV relevant AD risk factors. APOE4 is the greatest genetic risk factor for sporadic AD especially in women and is associated with CV dysfunction. EFAD mice express human APOE3 (E3FAD) or APOE4 (E4FAD), overproduce human Aβ42 and are a well characterized model of APOE pathology. Thus, initially the role of APOE and sex in cognitive and CV dysfunction was assessed in EFAD mice in order to identify a group for EGF treatment. At 8 months E4FAD female mice were cognitively impaired, had low CV coverage, high microbleeds and low plasma EGF levels. Therefore, E4FAD female mice were selected for an EGF prevention paradigm (300 μg/kg/wk, 6 to 8.5 months). EGF prevented cognitive decline and was associated with lower microbleeds and higher CV coverage, but not changes in Aβ levels. Collectively, these data suggest that EGF can prevent Aβ-induced damage to the CV. Developing therapeutic strategies based on AGFs may be particularly efficacious for APOE4-induced AD risk.Electronic supplementary materialThe online version of this article (doi:10.1186/s40478-016-0387-3) contains supplementary material, which is available to authorized users.

show abstract

Section: Introductionmentioning

confidence: 99%

Epidermal growth factor prevents APOE4 and amyloid-beta-induced cognitive and cerebrovascular deficits in female mice

Thomas

Zuchowska

Morris

et al. 2016

acta neuropathol commun

104

View full text Add to dashboard Cite

show abstract

“…The indication for Aβ-related angiogenesis has been extended in vivo as well, which can be observed with the chick embryo chorioallantoic membrane assay [65]. Aβ1-40 and Aβ1-42 stimulated embryos illustrated escalated vascular growth [65].…”

Section: Angiogenesis: Inflammation and Vascular Activationmentioning

confidence: 88%

“…Aβ1-40 and Aβ1-42 stimulated embryos illustrated escalated vascular growth [65]. In vivo studies, using various APP mutant AD mouse models that have an overproduction of Aβ, show modifications in brain vasculature compared to the wild-type animals [12,25].…”

Section: Angiogenesis: Inflammation and Vascular Activationmentioning

confidence: 99%

“…It was observed that that AD brain capillaries contained pre-amyloid deposits [60]. Aβ stimulates angiogenesis in a highly conserved manner, which is speculated to be mediated through γ-secretase activity and Notch signalling [60,65]. The in vitro studies of human umbilical vein endothelial cells (hUVEC), exposed directly to Aβ1-40 and Aβ1-42, show an angiogenic effect on the hUVEC, which exhibited an increase in the number of tip cells and branching [60].…”

Section: Angiogenesis: Inflammation and Vascular Activationmentioning

confidence: 99%

See 1 more Smart Citation

Pathogenic Angiogenic Mechanisms in Alzheimer's Disease

Singh¹,

Pfeifer²,

Jefferies³

2017

Physiologic and Pathologic Angiogenesis - Signaling Mechanisms and Targeted Therapy

View full text Add to dashboard Cite

Vascular dysfunction is a crucial pathological hallmark of Alzheimer's disease (AD). Studies have reported that beta amyloid (Aβ) causes increased blood vessel growth in the brains of AD mouse models, a phenomenon that is also seen in AD patients. This has given way to an alternative angiogenesis hypothesis according to which, increased leakiness in the blood vessels disrupts the blood-brain barrier (BBB) and allows unwanted blood products to enter the brain causing progression of disease pathology, promoting amyloid clumping and aggregation along with impaired cerebral blood flow. Furthermore, the expression of melanotransferrin in AD model and patients may contribute to angiogenesis. The objective of this chapter is to attempt to establish a link between the vascular damage and AD pathology. Curbing the vascular changes and resulting damage seen in the brains of AD model mice and improving their cognition by treating with FDA-approved anti-angiogenic drugs may expedite the translational potential of this research into clinical trials in human patients. This direction into targeting angiogenesis will facilitate new preventive and therapeutic interventions for AD and related vascular diseases.

show abstract

“…Diagnosis is difficult, as many neurodegenerative conditions present with a similar picture [1]. Amyloid beta (Aȕ) is a normal product of metabolism, cleaved from an amyloid precursor protein (APP) [2].…”

Section: Introductionmentioning

confidence: 99%

Blood vessel feature description for detection of Alzheimers disease

Sahrim

Nixon

Carare

2014

2014 13th International Conference on Control Automation Robotics &Amp; Vision (ICARCV)

View full text Add to dashboard Cite

Abstract-We describe how image analysis can be used to detect the presence of Alzheimer's disease. The data are images of brain tissue collected from subjects with and without Alzheimer's disease. The analysis concentrates on the shape and structure of the blood vessels which are known to be affected by amyloid beta, whose drainage is affected by Alzheimer's disease. The structure is analysed by a new approach which measures the Influence of the blood vessels' branching structures. Their density and tortuosity are analysed in conjunction with a boundary description derived using Fourier descriptors. These measures form a feature vector which is derived from the images of brain tissue, and the discrimination capability shows that it is possible to detect the presence of Alzheimer's disease using these measures and in an automated way. These measures also show that shape information is influenced by the vessels' branching structure, as known to be consistent with Alzheimer's disease evolution.

show abstract

β amyloid angiogenic activity in vitro and in vivo

Cited by 33 publications

References 18 publications

Epidermal growth factor prevents APOE4 and amyloid-beta-induced cognitive and cerebrovascular deficits in female mice

Epidermal growth factor prevents APOE4 and amyloid-beta-induced cognitive and cerebrovascular deficits in female mice

Pathogenic Angiogenic Mechanisms in Alzheimer's Disease

Blood vessel feature description for detection of Alzheimers disease

Contact Info

Product

Resources

About