Journal
MOLECULAR PSYCHIATRY
Volume 26, Issue 3, Pages 888-896Publisher
SPRINGERNATURE
DOI: 10.1038/s41380-019-0458-5
Keywords
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Funding
- NCATS NIH HHS [UL1 TR000445] Funding Source: Medline
- NIA NIH HHS [P50 AG025711, P30 AG019610, K01 AG049164, R01 AG034962, R01 AG018023, U01 AG006786, R01 AG015819, P01 AG003949, U01 AG046139, K24 AG046373, R01 AG056534, P50 AG016574, U01 AG046170, R01 AG061518, R01 AG017917, R01 AG059716, U01 AG046152, P01 AG017216, R01 AG032990, P30 AG010161] Funding Source: Medline
- NICHD NIH HHS [K12 HD043483] Funding Source: Medline
- NIH HHS [S10 OD023680] Funding Source: Medline
- NINDS NIH HHS [R01 NS080820, R01 NS100980, U24 NS072026] Funding Source: Medline
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The study revealed that the VEGF gene family plays a complex role in neuroprotection and is associated with cognitive performance, cognitive decline, and Alzheimer's disease pathology.
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. beta-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 beta-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.
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