2. Academic Validation
  3. Identification of a peptide recognizing cerebrovascular changes in mouse models of Alzheimer's disease

Identification of a peptide recognizing cerebrovascular changes in mouse models of Alzheimer's disease

  • Nat Commun. 2017 Nov 10;8(1):1403. doi: 10.1038/s41467-017-01096-0.
Aman P Mann 1,  Pablo Scodeller 1 2,  Sazid Hussain 1 3,  Gary B Braun 1,  Tarmo Mölder 2,  Kadri Toome 2,  Rajesh Ambasudhan 4,  Tambet Teesalu 2,  Stuart A Lipton 4 5,  Erkki Ruoslahti 6 7
Affiliations

Affiliations

  • 1 Cancer Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, 92037, USA.
  • 2 Laboratory of Cancer Biology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, 50411, Estonia.
  • 3 AivoCode Inc., La Jolla, CA, 92037, USA.
  • 4 Neurodegenerative Disease Center, Scintillon Institute, San Diego, CA, 92121, USA.
  • 5 Department of Neurosciences, University of California, San Diego, School of Medicine, La Jolla, CA, 92093, USA.
  • 6 Cancer Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, 92037, USA. ruoslahti@sbpdiscovery.org.
  • 7 Center for Nanomedicine and Department of Cell, Molecular and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA, 93106, USA. ruoslahti@sbpdiscovery.org.
PMID: 29123083 DOI: 10.1038/s41467-017-01096-0
Abstract

Cerebrovascular changes occur in Alzheimer's disease (AD). Using in vivo phage display, we searched for molecular markers of the neurovascular unit, including endothelial cells and astrocytes, in mouse models of AD. We identified a cyclic peptide, CDAGRKQKC (DAG), that accumulates in the hippocampus of hAPP-J20 mice at different ages. Intravenously injected DAG peptide homes to neurovascular unit endothelial cells and to reactive astrocytes in mouse models of AD. We identified connective tissue growth factor (CTGF), a matricellular protein that is highly expressed in the brain of individuals with AD and in mouse models, as the target of the DAG peptide. We also showed that exogenously delivered DAG homes to the brain in mouse models of glioblastoma, traumatic brain injury, and Parkinson's disease. DAG may potentially be used as a tool to enhance delivery of therapeutics and imaging agents to sites of vascular changes and astrogliosis in diseases associated with neuroinflammation.

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