DOI: 10.1523/jneurosci.0297-04.2004. Neuronal Zinc Exchange with the Blood Vessel Wall Promotes Cerebral Amyloid Angiopathy in an Animal Model of Alzheimer's Disease

Neuronal Zinc Exchange with the Blood Vessel Wall Promotes Cerebral Amyloid Angiopathy in an Animal Model of Alzheimer's Disease

10.1523/jneurosci.0297-04.2004

Crossref journal-article

Society for Neuroscience

The Journal of Neuroscience (393)

Abstract

Cerebral amyloid angiopathy (CAA) is common in Alzheimer's disease (AD) and may contribute to dementia and cerebral hemorrhage. Parenchymal β-amyloid deposition is dependent on the activity of zinc transporter 3 (ZnT3), a neocortical synaptic vesicle membrane protein that causes enrichment of exchangeable Zn2+in the vesicle, which is externalized on neurotransmission. However, the contribution of zinc to vascular β-amyloid deposition remains unclear. Here, we identify for the first time an exchangeable pool of Zn2+in the cerebrovascular wall of normal mice. This histochemically reactive Zn2+is enriched in CAA in a transgenic mouse model of AD (Tg2576), and a dramatic reduction of CAA occurs after targeted disruption of theZnt3gene in these mice. Also, inZnt3knock-out mice, the amount of exchangeable Zn2+[detected byN-(6-methoxy-8-quinolyl)-p-carboxybenzoylsulphonamide (TFL-Zn)] in the perivascular space was significantly decreased in the neocortex but not in peripheral organs. ZnT3 was not detected in the cerebral vessel walls or in blood components of wild-type mice. Thus, synaptic ZnT3 activity may promote CAA by indirectly raising exchangeable Zn2+concentrations in the perivascular spaces of the brain.

Bibliography

Friedlich, A. L., Lee, J.-Y., van Groen, T., Cherny, R. A., Volitakis, I., Cole, T. B., Palmiter, R. D., Koh, J.-Y., & Bush, A. I. (2004). Neuronal Zinc Exchange with the Blood Vessel Wall Promotes Cerebral Amyloid Angiopathy in an Animal Model of Alzheimerâs Disease. The Journal of Neuroscience, 24(13), 3453â3459.

Authors 9

Avi L. Friedlich (first)
Joo-Yong Lee (additional)
Thomas van Groen (additional)
Robert A. Cherny (additional)
Irene Volitakis (additional)
Toby B. Cole (additional)
Richard D. Palmiter (additional)
Jae-Young Koh (additional)
Ashley I. Bush (additional)

References 51 Referenced 105

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Dates

Type	When
Created	21 years, 4 months ago (March 31, 2004, 3:47 p.m.)
Deposited	2 years, 4 months ago (April 13, 2023, 12:06 p.m.)
Indexed	11 months, 2 weeks ago (Sept. 12, 2024, 5:22 p.m.)
Issued	21 years, 5 months ago (March 31, 2004)
Published	21 years, 5 months ago (March 31, 2004)
Published Online	21 years, 5 months ago (March 31, 2004)
Published Print	21 years, 5 months ago (March 31, 2004)

Funders 0

None

BibTeX

@article{Friedlich_2004, title={Neuronal Zinc Exchange with the Blood Vessel Wall Promotes Cerebral Amyloid Angiopathy in an Animal Model of Alzheimer’s Disease}, volume={24}, ISSN={1529-2401}, url={http://dx.doi.org/10.1523/jneurosci.0297-04.2004}, DOI={10.1523/jneurosci.0297-04.2004}, number={13}, journal={The Journal of Neuroscience}, publisher={Society for Neuroscience}, author={Friedlich, Avi L. and Lee, Joo-Yong and van Groen, Thomas and Cherny, Robert A. and Volitakis, Irene and Cole, Toby B. and Palmiter, Richard D. and Koh, Jae-Young and Bush, Ashley I.}, year={2004}, month=mar, pages={3453–3459} }

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        [
          2004,
          3,
          31
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1523/JNEUROSCI.0297-04.2004"
  ],
  "URL": "http://dx.doi.org/10.1523/JNEUROSCI.0297-04.2004",
  "relation": {},
  "ISSN": [
    "0270-6474",
    "1529-2401"
  ],
  "subject": [],
  "container-title-short": "J. Neurosci.",
  "published": {
    "date-parts": [
      [
        2004,
        3,
        31
      ]
    ]
  }
}