Role of neuroinflammation in hypertension-induced brain amyloid pathology

Hypertension and sporadic Alzheimer's disease (AD) have been associated but clear pathophysiological links have not yet been demonstrated. Hypertension and AD share inflammation as a pathophysiological trait. Thus, we explored if modulating neuroinflammation could influence hypertension-induced beta-amyloid (A beta) deposition. Possible interactions among hypertension, inflammation and A beta-deposition were studied in hypertensive mice with transverse aortic coarctation (TAC). Given that brain A beta deposits are detectable as early as 4 weeks after TAC, brain pathology was analyzed in 3-week TAC mice, before A beta deposition, and at a later time (8-week TAC mice). Microglial activation and interleukin (IL)-1 beta upregulation were already found in 3-week TAC mice. At a later time, along with evident A beta deposition, microglia was still activated. Finally, immune system stimulation (LPS) or inhibition (ibuprofen), strategies described to positively or negatively modulate neuroinflammation, differently affected A beta deposition. We demonstrate that hypertension per se triggers neuroinflammation before A beta deposition. The finding that only immune system activation, but not its inhibition, strongly reduced amyloid burden suggests that stimulating inflammation in the appropriate time window may represent a promising strategy to limit vascular-triggered AD-pathology. (C) 2012 Elsevier Inc. All rights reserved.