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 β-amyloid (Aβ) deposition. Possible interactions among hypertension, inflammation and Aβ-deposition were studied in hypertensive mice with transverse aortic coarctation (TAC). Given that brain Aβ deposits are detectable as early as 4 weeks after TAC, brain pathology was analyzed in 3-week TAC mice, before Aβ deposition, and at a later time (8-week TAC mice). Microglial activation and interleukin (IL)-1β upregulation were already found in 3-week TAC mice. At a later time, along with evident Aβ deposition, microglia was still activated. Finally, immune system stimulation (LPS) or inhibition (ibuprofen), strategies described to positively or negatively modulate neuroinflammation, differently affected Aβ deposition. We demonstrate that hypertension per se triggers neuroinflammation before Aβ 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.
Carnevale
Daniela
D
Department of Angio-Cardio-Neurology, IRCCS Neuromed, 86,077 Pozzilli (IS), Italy. daniela.carnevale@neuromed.it
Mascio
Giada
G
Ajmone-Cat
Maria Antonietta
MA
D'Andrea
Ivana
I
Cifelli
Giuseppe
G
Madonna
Michele
M
Cocozza
Germana
G
Frati
Alessandro
A
Carullo
Pierluigi
P
Carnevale
Lorenzo
L
Alleva
Enrico
E
Branchi
Igor
I
Lembo
Giuseppe
G
Minghetti
Luisa
L
D000544:Alzheimer Disease / Q000209:etiology* / Q000473:pathology / Q000628:therapy; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D002560:Cerebrovascular Circulation / Q000502:physiology; D004195:Disease Models, Animal; D006973:Hypertension / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D007052:Ibuprofen / Q000008:administration & dosage; D007107:Immune System / Q000276:immunology; D053583:Interleukin-1beta / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000502:physiology; D020078:Neurogenic Inflammation / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D015854:Up-Regulation
D016229:Amyloid beta-Peptides; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D007052:Ibuprofen