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Mol Neurodegener. 2016 Mar 3;11:23. doi: 10.1186/s13024-016-0088-1.

The NLRP3 and NLRP1 inflammasomes are activated in Alzheimer's disease.

Author information

1
Don C. Gnocchi Foundation, IRCCS, Piazza Morandi, 3, 20121, Milan, Italy. msaresella@dongnocchi.it.
2
Don C. Gnocchi Foundation, IRCCS, Piazza Morandi, 3, 20121, Milan, Italy. flarosa@dongnocchi.it.
3
Don C. Gnocchi Foundation, IRCCS, Piazza Morandi, 3, 20121, Milan, Italy. fpiancone@dongnocchi.it.
4
Don C. Gnocchi Foundation, IRCCS, Piazza Morandi, 3, 20121, Milan, Italy. mzoppis@dongnocchi.it.
5
Don C. Gnocchi Foundation, IRCCS, Piazza Morandi, 3, 20121, Milan, Italy. imarventano@dongnocchi.it.
6
Don C. Gnocchi Foundation, IRCCS, Piazza Morandi, 3, 20121, Milan, Italy. ecalabrese@dongnocchi.it.
7
Departments of Biomedical and Clinical Sciences "Luigi Sacco", University of Milano, 20100, Milan, Italy. veronica.rainone@unimi.it.
8
Don C. Gnocchi Foundation, IRCCS, Piazza Morandi, 3, 20121, Milan, Italy. rnemni@dongnocchi.it.
9
Departments of Physiopathology and Transplants, University of Milano, 20100, Milan, Italy. rnemni@dongnocchi.it.
10
Don C. Gnocchi Foundation, IRCCS, Piazza Morandi, 3, 20121, Milan, Italy. rmancuso@dongnocchi.it.
11
Don C. Gnocchi Foundation, IRCCS, Piazza Morandi, 3, 20121, Milan, Italy. mario.clerici@unimi.it.
12
Departments of Physiopathology and Transplants, University of Milano, 20100, Milan, Italy. mario.clerici@unimi.it.

Abstract

BACKGROUND:

Interleukin-1 beta (IL-1β) and its key regulator, the inflammasome, are suspected to play a role in the neuroinflammation observed in Alzheimer's disease (AD); no conclusive data are nevertheless available in AD patients.

RESULTS:

mRNA for inflammasome components (NLRP1, NLRP3, PYCARD, caspase 1, 5 and 8) and downstream effectors (IL-1β, IL-18) was up-regulated in severe and MILD AD. Monocytes co-expressing NLRP3 with caspase 1 or caspase 8 were significantly increased in severe AD alone, whereas those co-expressing NLRP1 and NLRP3 with PYCARD were augmented in both severe and MILD AD. Activation of the NLRP1 and NLRP3 inflammasomes in AD was confirmed by confocal microscopy proteins co-localization and by the significantly higher amounts of the pro-inflammatory cytokines IL-1β and IL-18 being produced by monocytes. In MCI, the expression of NLRP3, but not the one of PYCARD or caspase 1 was increased, indicating that functional inflammasomes are not assembled in these individuals: this was confirmed by lack of co-localization and of proinflammatory cytokines production.

CONCLUSIONS:

The activation of at least two different inflammasome complexes explains AD-associated neuroinflammation. Strategies targeting inflammasome activation could be useful in the therapy of AD.

PMID:
26939933
PMCID:
PMC4778358
DOI:
10.1186/s13024-016-0088-1
[Indexed for MEDLINE]
Free PMC Article

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