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Evidence of angiogenic vessels in Alzheimer’s disease

  • Dementias - Original Article
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Abstract

Alterations in the blood brain barrier and brain vasculature may be involved in neurodegeneration and neuroinflammation. We sought to determine if vascular remodeling characterized by angiogenic vessels or increased vascular density, occurred in pathologically confirmed Alzheimer’s disease (AD) postmortem human brain tissues. We examined brains of deceased, older catholic clergy from the Religious Order Study, a longitudinal clinical–pathological study of aging and AD. The hippocampus, midfrontal cortex, substantia nigra, globus pallidus and locus ceruleus were examined for integrin αvβ3 immunoreactivity, a marker of angiogenesis, and vascular densities. Activated microglia cell counts were also performed. All areas except the globus pallidus exhibited elevated αvβ3 immunoreactivity in AD cases compared with controls. Only in the hippocampus did the ongoing angiogenesis result in increased vascular density compared with controls. Vascular density was correlated with Aβ load in the hippocampus and αvβ3 reactivity was correlated with neurofibrillary tangles in the midfrontal cortex and in the substantia nigra. These data indicate that ongoing angiogenesis is present in brain regions affected by AD pathology and may be related to tissue injury.

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Acknowledgments

This work was supported by RO1AI51619 (BH), K08AG00084 (JAS), P30AG10161 (JAS), R01AG15819 (JAS), and the Kenneth Douglas Foundation (PMC). We thank Dr. Sue Leurgans for her statistical expertise. We thank the nuns, priests, and brothers from the following groups participating in the Religious Orders Study: Archdiocesan priests of Chicago, Dubuque, and Milwaukee; Benedictine Monks, Lisle, IL, and Collegeville, MN; Benedictine Sisters of Erie, Erie, PA; Benedictine Sisters of the Sacred Heart, Lisle, IL; Capuchins, Appleton, WI; Christian Brothers, Chicago, IL, and Memphis, TN; Diocesan priests of Gary, IN; Dominicans, River Forest, IL; Felician Sisters, Chicago, IL; Franciscan Handmaids of Mary, New York, NY; Franciscans, Chicago, IL; Holy Spirit Missionary Sisters, Techny, IL; Maryknolls, Los Altos, CA and Maryknoll, NY; Norbertines, DePere, WI; Oblate Sisters of Providence, Baltimore, MD; Passionists, Chicago, IL; Presentation Sisters, Dubuque, BVM., IA; Servites, Chicago, IL; Sinsinawa Dominican Sisters, Chicago, IL, and Sinsinawa, WI; Sisters of Charity, B.V.M., Chicago, IL, and Dubuque, IA; Sisters of the Holy Family, New Orleans, LA; Sisters of the Holy Family of Nazareth, Des Plaines, IL; Sisters of Mercy of the Americas, Chicago and Aurora, IL, Erie, PA; Sisters of St. Benedict, St. Cloud and St. Joseph, MN; Sisters of St. Casimir, Chicago, IL; Sisters of St. Francis of Mary Immaculate, Joliet, IL; Sisters of St. Joseph of LaGrange, LaGrange Park, IL; Society of Divine Word, Techny, IL; Trappists, Gethsemani, KY, and Peosta, IA; Wheaton Franciscan Sisters, Wheaton, IL. We thank T. Colvin and J. Bach, Religious Orders Study Coordinators; data and analytic programmers, Karen Skish, Veronica Flores, Davik Shah, Benjamin Spirtovic, Wayne Longman and Yu Li for technical assistance and the Rush Institute for Healthy Aging staff.

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Authors and Affiliations

  1. Department of Pharmacology, Rush University Medical Center, Cohn Research Building, 1735 W Harrison Suite 412, Chicago, IL, 60612, USA

    Brinda S. Desai, Paul M. Carvey & Bill Hendey

  2. Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, IL, 60612, USA

    Julie A. Schneider & Jia-Liang Li

  3. Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, 60612, USA

    Julie A. Schneider, Jia-Liang Li & Paul M. Carvey

  4. Department of Pathology, Rush University Medical Center, Chicago, IL, 60612, USA

    Julie A. Schneider

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  1. Brinda S. Desai
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  5. Bill Hendey
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Correspondence to Bill Hendey.

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Desai, B.S., Schneider, J.A., Li, JL. et al. Evidence of angiogenic vessels in Alzheimer’s disease. J Neural Transm 116, 587–597 (2009). https://doi.org/10.1007/s00702-009-0226-9

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