%0 Journal Article %J J Alzheimers Dis %D 2020 %T Novel Markers of Angiogenesis in the Setting of Cognitive Impairment and Dementia. %A Callahan, Christopher M %A Apostolova, Liana G %A Gao, Sujuan %A Risacher, Shannon L %A Case, Jamie %A Saykin, Andrew J %A Lane, Kathleen A %A Swinford, Cecily G %A Yoder, Mervin C %X

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.

%B J Alzheimers Dis %V 75 %P 959-969 %8 2020 Jun 02 %G eng %N 3 %R 10.3233/JAD-191293 %0 Journal Article %J J Alzheimers Dis %D 2015 %T Comprehensive Gene- and Pathway-Based Analysis of Depressive Symptoms in Older Adults. %A Nho, Kwangsik %A Ramanan, Vijay K %A Horgusluoglu, Emrin %A Kim, Sungeun %A Inlow, Mark H %A Risacher, Shannon L %A McDonald, Brenna C %A Farlow, Martin R %A Foroud, Tatiana M %A Gao, Sujuan %A Callahan, Christopher M %A Hendrie, Hugh C %A Niculescu, Alexander B %A Saykin, Andrew J %X

Depressive symptoms are common in older adults and are particularly prevalent in those with or at elevated risk for dementia. Although the heritability of depression is estimated to be substantial, single nucleotide polymorphism-based genome-wide association studies of depressive symptoms have had limited success. In this study, we PERFORMED genome-wide gene- and pathway-based analyses of depressive symptom burden. Study participants included non-Hispanic Caucasian subjects (n = 6,884) from three independent cohorts, the Alzheimer's Disease Neuroimaging Initiative (ADNI), the Health and Retirement Study (HRS), and the Indiana Memory and Aging Study (IMAS). Gene-based meta-analysis identified genome-wide significant associations (ANGPT4 and FAM110A, q-value = 0.026; GRM7-AS3 and LRFN5, q-value = 0.042). Pathway analysis revealed enrichment of association in 105 pathways, including multiple pathways related to ERK/MAPK signaling, GSK3 signaling in bipolar disorder, cell development, and immune activation and inflammation. GRM7, ANGPT4, and LRFN5 have been previously implicated in psychiatric disorders, including the GRM7 region displaying association with major depressive disorder. The ERK/MAPK signaling pathway is a known target of antidepressant drugs and has important roles in neuronal plasticity, and GSK3 signaling has been previously implicated in Alzheimer's disease and as a promising therapeutic target for depression. Our results warrant further investigation in independent and larger cohorts and add to the growing understanding of the genetics and pathobiology of depressive symptoms in aging and neurodegenerative disorders. In particular, the genes and pathways demonstrating association with depressive symptoms may be potential therapeutic targets for these symptoms in older adults.

%B J Alzheimers Dis %8 2015 Feb 17 %G ENG %1 http://www.ncbi.nlm.nih.gov/pubmed/25690665?dopt=Abstract %R 10.3233/JAD-148009