Vascular endothelial growth factor in Alzheimer's disease and experimental cerebral ischemia

Kalaria, Rajesh N.; Cohen, D. L.; Premkumar, Daniel R.; Nag, Sukriti; LaManna, Joseph Charles; Lust, W. David

doi:10.1016/s0169-328x(98)00190-9

Cited by 176 publications

(139 citation statements)

References 21 publications

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“…VEGFR2 was previously identified in astrocytes under hypoxic conditions [63,64], and in a subset of astrocytes in AD [29] and in human post-mortem brain tissue from patients with small vessel disease and controls [65]. VEGFR1 was reported to play a role in microglial chemotaxis and proliferation [42,66].…”

Section: Discussionmentioning

confidence: 99%

“…It is upregulated in response to hypoxia [27,28] and elevated within hypoperfused cortex and white matter in small vessel disease, vascular dementia and AD [3,[29][30][31][32]. Its effects are mediated by the tyrosine kinase receptors, vascular endothelial growth factor receptors 1 and 2 (VEGFR1 and VEGFR2), neuropilin (NRP1 and NRP2) and heparan sulfate proteoglycans (HSPGs) co-receptors.…”

Section: Introductionmentioning

confidence: 99%

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VEGFR1 and VEGFR2 in Alzheimer’s Disease

Harris

Miners

Allen

et al. 2017

JAD

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

VEGFR1 and VEGFR2 in Alzheimer’s Disease

Harris

Miners

Allen

et al. 2017

JAD

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“…In experimental stroke models, it has been reported that VEGFR-2 expression increases as early as 6 h after middle cerebral artery occlusion with peak activity observed after 5 to 7 days, whereas VEGF expression returned to near normal levels after 3 weeks. The 40% to 50% increased neuronal expression of VEGFR-2 in both ST and LT CH groups suggests a severe and prolonged stimulation in the neurons, similar to other chronic neurologic diseases, such as Parkinson's and Alzheimer's disease (Issa et al 1999;Kalaria et al, 1998). Although hypoxia can persist in CH, VEGFR-2 stimulation may originate from other sources as well (see below).…”

Section: Vascular Endothelial Growth Factor Receptor-2 Expressionmentioning

confidence: 82%

Dissociation between Vascular Endothelial Growth Factor Receptor-2 and Blood Vessel Density in the Caudate Nucleus after Chronic Hydrocephalus

Deshpande

Dombrowski

Leichliter

et al. 2009

J Cereb Blood Flow Metab

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Chronic hydrocephalus (CH) is characterized by the presence of ventricular enlargement, decreased cerebral blood flow (CBF), and brain tissue oxygen delivery. Although the underlying pathophysiological role of vascular endothelial growth factor (VEGF) is not clear, ischemic-hypoxic events in CH are known to trigger its release. Previously, we have shown increased VEGF receptor-2 (VEGFR-2) and blood vessel density (BVd) in the hippocampus after CH. We investigated changes in neuronal and glial VEGFR-2 density and BVd in the caudate nucleus in an experimental model of CH. Animals with CH were divided into short term (ST, 2 to 4 weeks) and long term (LT, 12 to 16 weeks) and were compared with surgical controls (SCs, 12 to 16 weeks). The cellular and BVds were estimated using immunohistochemical and stereological counting methods. Overall, percentage (%)VEGFR-2 neurons were approximately two times greater in CH (ST, LT) than in SC. By comparison, glial cell %VEGFR-2 was greater by 10% to 17% in ST and 4% to 11% lower in LT compared with that in SC. Blood vessel density was significantly lower in CH than in SC in the superficial caudate. Changes in cerebrospinal fluid ventricular volume and pressure, as well as in CBF did not correlate with either VEGFR-2 or BVd. These observed findings suggest that destructive forces may outweigh angiogenic forces and possibly show a disassociation between VEGFR-2 and BV expressions.

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“…Therefore, it is probable that reduction or complete loss of estrogen and progesterone can lead to increased hyperphosphorylation of τ (illustrated in Figure 3) and an increase in β-amyloid, which, in turn, also reinforces hyperphosphorylation resulting in the onset of AD. Since the loss of E2 concurrently produces a loss of P4, the body will experience diminished immunosuppression and loss of Vascular Endothelial Growth Factor (VEGF) [57].…”

Section: The τ Hyperphosphorylation and β-Amyloid Plaquesmentioning

confidence: 99%

Cyclic E2 and P4 on Alzheimer’s Disease Pathways

Wiley¹,

Haraldsen²

2017

AAD

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In recent years, Alzheimer's disease has been clearly linked to the degradation of microtubules and microtubule-associated tau (τ) and β-amyloid (βA) proteins. Through an examination and evaluation of current literature, we assess the possible effects of the steroid hormones on τ hyperphosphorylation and the regulation of βA proteins and their influence on Alzheimer's dementia and memory loss. We present a mechanism by which Alzheimer's cases may be reduced or perhaps even prevented through the use of non-synthetic, steroid hormones prescribed in a cyclic dosing schedule that mimics the rhythmic, escalating and descending production normally observed in a reproductive female body. Given the ability of estrogen to prevent τ hyperphosphorylation and increase metabolism of the βA precursor protein, we propose the possibility of controlling both protein cycles through the exogenous application of estrogen and progesterone may help those patients with active disease as well as prevent the onset of Alzheimer's and other neurodegenerative diseases.

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Vascular endothelial growth factor in Alzheimer's disease and experimental cerebral ischemia

Cited by 176 publications

References 21 publications

VEGFR1 and VEGFR2 in Alzheimer’s Disease

VEGFR1 and VEGFR2 in Alzheimer’s Disease

Dissociation between Vascular Endothelial Growth Factor Receptor-2 and Blood Vessel Density in the Caudate Nucleus after Chronic Hydrocephalus

Cyclic E2 and P4 on Alzheimer’s Disease Pathways

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