Cerebral amyloid angiopathy increases susceptibility to infarction after focal cerebral ischemia in Tg2576 mice.

Abstract

BACKGROUND AND PURPOSE:

We and others have shown that soluble amyloid β-peptide (Aβ) and cerebral amyloid angiopathy (CAA) cause significant cerebrovascular dysfunction in mutant amyloid precursor protein (APP) mice, and that these deficits are greater in aged APP mice having CAA compared with young APP mice lacking CAA. Amyloid β-peptide in young APP mice also increases infarction after focal cerebral ischemia, but the impact of CAA on ischemic brain injury is unknown.

METHODS:

To determine this, we assessed cerebrovascular reactivity, cerebral blood flow (CBF), and extent of infarction and neurological deficits after transient middle cerebral artery occlusion in aged APP mice having extensive CAA versus young APP mice lacking CAA (and aged-matched littermate controls).

RESULTS:

We found that aged APP mice have more severe cerebrovascular dysfunction that is CAA dependent, have greater CBF compromise during and immediately after middle cerebral artery occlusion, and develop larger infarctions after middle cerebral artery occlusion.

CONCLUSIONS:

These data indicate CAA induces a more severe form of cerebrovascular dysfunction than amyloid β-peptide alone, leading to intra- and postischemic CBF deficits that ultimately exacerbate cerebral infarction. Our results shed mechanistic light on human studies identifying CAA as an independent risk factor for ischemic brain injury.

• Authors: Eric Milner, Meng-Liang Zhou, Andrew W Johnson, Ananth K Vellimana, Jacob K Greenberg, David M Holtzman, Byung Hee Han, Gregory J Zipfel
• Journal: Stroke (Stroke) Vol. 45 Issue 10 Pg. 3064-9 (Oct 2014) ISSN: 1524-4628 [Electronic] United States
• PMID: 25190447 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 American Heart Association, Inc.

Topics

• Animals
• Brain (blood supply, pathology)
• Brain Ischemia (complications)
• Cerebral Amyloid Angiopathy (complications, physiopathology)
• Cerebral Infarction (etiology)
• Disease Susceptibility
• Male
• Mice
• Mice, Transgenic