| First Author | Friedlich AL | Year | 2004 |
| Journal | J Neurosci | Volume | 24 |
| Issue | 13 | Pages | 3453-9 |
| PubMed ID | 15056725 | Mgi Jnum | J:129255 |
| Mgi Id | MGI:3768947 | Doi | 10.1523/JNEUROSCI.0297-04.2004 |
| Citation | Friedlich AL, et al. (2004) Neuronal zinc exchange with the blood vessel wall promotes cerebral amyloid angiopathy in an animal model of Alzheimer's disease. J Neurosci 24(13):3453-9 |
| abstractText | Cerebral amyloid angiopathy (CAA) is common in Alzheimer's disease (AD) and may contribute to dementia and cerebral hemorrhage. Parenchymal beta-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 beta-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 the Znt3 gene in these mice. Also, in Znt3 knock-out mice, the amount of exchangeable Zn2+ [detected by N-(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. |
