Dataset Information

Brain expression of the vascular endothelial growth factor gene family in cognitive aging and alzheimer's disease.

ABSTRACT: Vascular endothelial growth factor (VEGF) is associated with the clinical manifestation of Alzheimer's disease (AD). However, the role of the VEGF gene family in neuroprotection is complex due to the number of biological pathways they regulate. This study explored associations between brain expression of VEGF genes with cognitive performance and AD pathology. Genetic, cognitive, and neuropathology data were acquired from the Religious Orders Study and Rush Memory and Aging Project. Expression of ten VEGF ligand and receptor genes was quantified using RNA sequencing of prefrontal cortex tissue. Global cognitive composite scores were calculated from 17 neuropsychological tests. ?-amyloid and tau burden were measured at autopsy. Participants (n?=?531) included individuals with normal cognition (n?=?180), mild cognitive impairment (n?=?148), or AD dementia (n?=?203). Mean age at death was 89 years and 37% were male. Higher prefrontal cortex expression of VEGFB, FLT4, FLT1, and PGF was associated with worse cognitive trajectories (p???0.01). Increased expression of VEGFB and FLT4 was also associated with lower cognition scores at the last visit before death (p???0.01). VEGFB, FLT4, and FLT1 were upregulated among AD dementia compared with normal cognition participants (p???0.03). All four genes associated with cognition related to elevated ?-amyloid (p???0.01) and/or tau burden (p???0.03). VEGF ligand and receptor genes, specifically genes relevant to FLT4 and FLT1 receptor signaling, are associated with cognition, longitudinal cognitive decline, and AD neuropathology. Future work should confirm these observations at the protein level to better understand how changes in VEGF transcription and translation relate to neurodegenerative disease.

SUBMITTER: Mahoney ER

PROVIDER: S-EPMC6980445 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Brain expression of the vascular endothelial growth factor gene family in cognitive aging and alzheimer's disease.

Mahoney Emily R ER Dumitrescu Logan L Moore Annah M AM Cambronero Francis E FE De Jager Philip L PL Koran Mary Ellen I MEI Petyuk Vladislav A VA Robinson Renã A S RAS Goyal Sandeep S Schneider Julie A JA Bennett David A DA Jefferson Angela L AL Hohman Timothy J TJ

Molecular psychiatry 20190722 3

Vascular endothelial growth factor (VEGF) is associated with the clinical manifestation of Alzheimer's disease (AD). However, the role of the VEGF gene family in neuroprotection is complex due to the number of biological pathways they regulate. This study explored associations between brain expression of VEGF genes with cognitive performance and AD pathology. Genetic, cognitive, and neuropathology data were acquired from the Religious Orders Study and Rush Memory and Aging Project. Expression of ...[more]

PMID: 31332262

Similar Datasets

Project description:Axotomy of central neurons leads to functional and structural alterations which largely revert when neural progenitor cells (NPCs) are implanted in the lesion site. The new microenvironment created by NPCs in the host tissue might modulate in the damaged neurons the expression of a high variety of molecules with relevant roles in the repair mechanisms, including neurotrophic factors. In the present work, we aimed to analyze changes in neurotrophic factor expression in axotomized neurons induced by NPC implants. For this purpose, we performed immunofluorescence followed by confocal microscopy analysis for the detection of vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and nerve growth factor (NGF) on brainstem sections from rats with axotomy of abducens internuclear neurons that received NPC implants (implanted group) or vehicle injections (axotomized group) in the lesion site. Control abducens internuclear neurons were strongly immunoreactive to VEGF and BDNF but showed a weak staining for NT-3 and NGF. Comparisons between groups revealed that lesioned neurons from animals that received NPC implants showed a significant increase in VEGF content with respect to animals receiving vehicle injections. However, the immunoreactivity for BDNF, which was increased in the axotomized group as compared to control, was not modified in the implanted group. The modifications induced by NPC implants on VEGF and BDNF content were specific for the population of axotomized abducens internuclear neurons since the neighboring abducens motoneurons were not affected. Similar levels of NT-3 and NGF immunolabeling were obtained in injured neurons from axotomized and implanted animals. Among all the analyzed neurotrophic factors, only VEGF was expressed by the implanted cells in the lesion site. Our results point to a role of NPC implants in the modulation of neurotrophic factor expression by lesioned central neurons, which might contribute to the restorative effects of these implants.

Dataset Information

Brain expression of the vascular endothelial growth factor gene family in cognitive aging and alzheimer's disease.

Publications

Brain expression of the vascular endothelial growth factor gene family in cognitive aging and alzheimer's disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets