Novel Markers of Angiogenesis in the Setting of Cognitive Impairment and Dementia

Article type: Research Article

Authors: Callahan, Christopher M.^{a; b; c; d; e; *} | Apostolova, Liana G.^{e; f; g} | Gao, Sujuan^{e; h} | Risacher, Shannon L.^{e; g} | Case, Jamieⁱ | Saykin, Andrew J.^{e; f; g; j} | Lane, Kathleen A.^h | Swinford, Cecily G.^{e; g} | Yoder, Mervin C.^k

Affiliations: [a] Indiana University Center for Aging Research, Indianapolis, IN, USA | [b] Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA | [c] Regenstrief Institute, Inc., Indianapolis, IN, USA | [d] Eskenazi Health, Indianapolis, IN, USA | [e] Indiana Alzheimer Disease Center, Indianapolis, IN, USA | [f] Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, USA | [g] Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA | [h] Department of Biostatistics, Indiana University School of Medicine, Indianapolis, IN, USA | [i] Scripps Clinic Bio-Repository and Bio-Informatics Core, Scripps Clinic Medical Group, La Jolla, CA, USA | [j] Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA | [k] Indiana Center for Regenerative Medicine and Engineering, Indiana University School of Medicine, Indianapolis, IN, USA | Institution of Origin: Indiana University School of Medicine, Indianapolis, IN, USA

Correspondence: [*] Correspondence to: Christopher M. Callahan, MD, Indiana University Center for Aging Research, 1101 West 10th Street, Indianapolis, IN 46202, USA. Tel.: +1 317 274 9050; E-mail: [email protected].

Abstract: Background:Aberrant angiogenesis may play a role in the development of Alzheimer’s disease and related dementia. Objective:To explore the relationship between angiogenesis activity and evidence of neurodegeneration among older adults. Methods:Cross-sectional study of 49 older adults clinically characterized as cognitively normal, mild cognitive impairment, or early Alzheimer’s disease. In addition to neuroimaging, we completed assays on peripheral blood, including: vascular endothelial growth factor, tumor necrosis factor, fibroblast growth factor, and amyloid-β peptide 40. We used advanced polychromatic flow cytometry to phenotype circulating mononuclear cells to assess angiogenesis activity. Results:Although we documented differences in cognitive performance, structural changes on neuroimaging, and burden of amyloid and tau on positron emission tomography, angiogenesis activity did not vary by group. Interestingly, VEGF levels were shown to be increased among subjects with mild cognitive impairment. In ANCOVA models controlling for age, sex, intracranial volume, and monocyte subpopulations, angiogenesis activity was correlated with increased white matter hyperintensities. Conclusion:We demonstrate a significant association between angiogenesis activity and cerebrovascular disease. To better understand the potential of angiogenesis as an intervention target, longitudinal studies are needed.

Keywords: Alzheimer’s disease, biomarkers, pathologic angiogenesis, vascular dementia

DOI: 10.3233/JAD-191293

Journal: Journal of Alzheimer's Disease, vol. 75, no. 3, pp. 959-969, 2020