Brain expression of the vascular endothelial growth factor gene family in cognitive aging and alzheimer’s disease
[2];
[4];
[1]
- Vanderbilt Univ., Nashville, TN (United States)
- Columbia University Medical Center, New York, NY (United States); Cell Circuits Program, Broad Institute, Cambridge, MA (United States)
- Stanford Univ., CA (United States)
- Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
- Rush University Medical Center, Chicago, IL (United States)
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. β-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 β-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.
- Research Organization:
- Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
- Sponsoring Organization:
- USDOE
- Grant/Contract Number:
- AC05-76RL01830
- OSTI ID:
- 1779283
- Report Number(s):
- PNNL-SA-147565
- Journal Information:
- Molecular Psychiatry, Vol. 26, Issue 3; ISSN 1359-4184
- Publisher:
- SpringerCopyright Statement
- Country of Publication:
- United States
- Language:
- English
PLD3 is a neuronal lysosomal phospholipase D associated with β‐amyloid plaques and cognitive function in Alzheimer’s disease: Molecular and cell biology/enzyme activities
|
journal | December 2020 |
Gender Related Changes in Gene Expression Induced by Valproic Acid in A Mouse Model of Autism and the Correction by S-adenosyl Methionine. Does It Explain the Gender Differences in Autistic Like Behavior?
|
journal | October 2019 |
Similar Records
Association of Cortical ß-Amyloid Protein in the Absence of Insoluble Deposits With Alzheimer Disease.
Assessment of Demographic, Genetic, and Imaging Variables Associated With Brain Resilience and Cognitive Resilience to Pathological Tau in Patients With Alzheimer Disease