Doxycycline counteracts neuroinflammation restoring memory in Alzheimer's disease mouse models

Claudia Balducci, Giulia Santamaria, Pietro La Vitola, Edoardo Brandi, Federica Grandi, Arturo Roberto Viscomi, Marten Beeg, Marco Gobbi, Mario Salmona, Simone Ottonello, Gianluigi Forloni

Research output: Contribution to journalArticle

Abstract

β-Amyloid oligomers (AβOs) and neuroinflammation are 2 main culprits to counteract in Alzheimer's disease (AD). Doxycycline (DOXY) is a second generation antibiotic of the tetracycline class that are promising drugs tested in many clinical trials for a number of different pathologies. DOXY is endowed with antiamyloidogenic properties and better crosses the blood-brain barrier, but its efficacy has never been tested in AD mice. We herein show that 15- to 16-month-old APP/PS1dE9 (APP/PS1) AD mice receiving DOXY under different treatment regimens recovered their memory without plaque reduction. An acute DOXY treatment was, also, sufficient to improve APP/PS1 mouse memory, suggesting an action against soluble AβOs. This was confirmed in an AβO-induced mouse model, where the AβO-mediated memory impairment was abolished by a DOXY pretreatment. Although AβOs induce memory impairment through glial activation, assessing the anti-inflammatory action of DOXY, we found that in both the AβO-treated and APP/PS1 mice, the memory recovery was associated with a lower neuroinflammation. Our data promote DOXY as a hopeful repositioned drug counteracting crucial neuropathological AD targets.

Original languageEnglish
Pages (from-to)128-139
Number of pages12
JournalNeurobiology of Aging
Volume70
DOIs
Publication statusPublished - Oct 2018

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