Role of neuroinflammation in hypertension-induced brain amyloid pathology

Daniela Carnevale, Giada Mascio, Maria Antonietta Ajmone-Cat, Ivana D'Andrea, Giuseppe Cifelli, Michele Madonna, Germana Cocozza, Alessandro Frati, Pierluigi Carullo, Lorenzo Carnevale, Enrico Alleva, Igor Branchi, Giuseppe Lembo, Luisa Minghetti

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
JournalNeurobiology of Aging
Volume33
Issue number1
DOIs
Publication statusPublished - Jan 2012

Keywords

  • Alzheimer's disease
  • Cerebral hemodynamics
  • Glial cells
  • Hypertension
  • Inflammation

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Ageing
  • Developmental Biology
  • Geriatrics and Gerontology

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