The role of vascular endothelial growth factor in neurodegeneration and cognitive decline: exploring interactions with biomarkers of Alzheimer disease

Timothy J Hohman; Susan P Bell; Angela L Jefferson; Alzheimer’s Disease Neuroimaging Initiative

doi:10.1001/jamaneurol.2014.4761

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The role of vascular endothelial growth factor in neurodegeneration and cognitive decline: exploring interactions with biomarkers of Alzheimer disease

Journal article

Open access

Peer reviewed

The role of vascular endothelial growth factor in neurodegeneration and cognitive decline: exploring interactions with biomarkers of Alzheimer disease

Timothy J Hohman, Susan P Bell, Angela L Jefferson and Alzheimer’s Disease Neuroimaging Initiative

JAMA neurology, Vol.72(5), pp.520-529

05/2015

DOI: 10.1001/jamaneurol.2014.4761

PMCID: PMC4428948

PMID: 25751166

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Abstract

A subset of older adults present post mortem with Alzheimer disease (AD) pathologic features but without any significant clinical manifestation of dementia. Vascular endothelial growth factor (VEGF) has been implicated in staving off AD-related neurodegeneration. To evaluate whether VEGF levels are associated with brain aging outcomes (hippocampal volume and cognition) and to further evaluate whether VEGF modifies relations between AD biomarkers and brain aging outcomes. Biomarker analysis using neuroimaging and neuropsychological outcomes from the Alzheimer's Disease Neuroimaging Initiative. This prospective longitudinal study across North America included individuals with normal cognition (n = 90), mild cognitive impairment (n = 130), and AD (n = 59) and began in October 2004, with follow-up ongoing. Cerebrospinal fluid VEGF was cross-sectionally related to brain aging outcomes (hippocampal volume, episodic memory, and executive function) using a general linear model and longitudinally using mixed-effects regression. Alzheimer disease biomarker (cerebrospinal fluid β-amyloid 42 and total tau)-by-VEGF interactions evaluated the effect of VEGF on brain aging outcomes in the presence of enhanced AD biomarkers. Vascular endothelial growth factor was associated with baseline hippocampal volume (t277 = 2.62; P = .009), longitudinal hippocampal atrophy (t858 = 2.48; P = .01), and longitudinal decline in memory (t1629 = 4.09; P < .001) and executive function (t1616 = 3.00; P = .003). Vascular endothelial growth factor interacted with tau in predicting longitudinal hippocampal atrophy (t845 = 4.17; P < .001), memory decline (t1610 = 2.49; P = .01), and executive function decline (t1597 = 3.71; P < .001). Vascular endothelial growth factor interacted with β-amyloid 42 in predicting longitudinal memory decline (t1618 = -2.53; P = .01). Elevated cerebrospinal fluid VEGF was associated with more optimal brain aging in vivo. The neuroprotective effect appeared strongest in the presence of enhanced AD biomarkers, suggesting that VEGF may be particularly beneficial in individuals showing early hallmarks of the AD cascade. Future work should evaluate the interaction between VEGF expression in vitro and pathologic burden to address potential mechanisms.

Humans

Atrophy - pathology

Vascular Endothelial Growth Factor A - cerebrospinal fluid

Memory, Episodic

Male

Aging - cerebrospinal fluid

Alzheimer Disease - pathology

Aged, 80 and over

Amyloid beta-Peptides - cerebrospinal fluid

Female

Alzheimer Disease - physiopathology

Peptide Fragments - cerebrospinal fluid

Cross-Sectional Studies

Hippocampus - pathology

tau Proteins - cerebrospinal fluid

Cognitive Dysfunction - cerebrospinal fluid

Cognitive Dysfunction - pathology

Alzheimer Disease - cerebrospinal fluid

Cognitive Dysfunction - physiopathology

Executive Function - physiology

Aging - pathology

Aging - physiology

Aged

Biomarkers - cerebrospinal fluid

Longitudinal Studies

Details

Title: Subtitle: The role of vascular endothelial growth factor in neurodegeneration and cognitive decline: exploring interactions with biomarkers of Alzheimer disease
Creators: Timothy J Hohman - Vanderbilt Memory & Alzheimer's Center, Vanderbilt University School of Medicine, Nashville, Tennessee
Susan P Bell - Vanderbilt Memory & Alzheimer's Center, Vanderbilt University School of Medicine, Nashville, Tennessee2Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee3Center for Quality Aging, Di
Angela L Jefferson - Vanderbilt Memory & Alzheimer's Center, Vanderbilt University School of Medicine, Nashville, Tennessee
Alzheimer’s Disease Neuroimaging Initiative
Contributors: Laura L Boles-Ponto (Contributor) - University of Iowa, Radiology
Resource Type: Journal article
Publication Details: JAMA neurology, Vol.72(5), pp.520-529
DOI: 10.1001/jamaneurol.2014.4761
PMID: 25751166
PMCID: PMC4428948
NLM abbreviation: JAMA Neurol
ISSN: 2168-6149
eISSN: 2168-6157
Publisher: United States
Grant note: P30 AG062421 / NIA NIH HHS P50 AG005134 / NIA NIH HHS U54 HD083211 / NICHD NIH HHS R01 AG034962 / NIA NIH HHS R01 HL111516 / NHLBI NIH HHS K23 AG048347 / NIA NIH HHS P30 AG013846 / NIA NIH HHS K12 HD043483 / NICHD NIH HHS K24 AG046373 / NIA NIH HHS U01 AG024904 / NIA NIH HHS L30 AG048601 / NIA NIH HHS
Language: English
Date published: 05/2015
Academic Unit: Radiology; Pharmaceutical Sciences and Experimental Therapeutics
Record Identifier: 9984051516402771

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