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TREM2 expression and amyloid‐beta phagocytosis in Alzheimer's disease

La Rosa, Francesca, Agostini, Simone, Piancone, Federica, Marventano, Ivana, Hernis, Ambra, Fenoglio, Chiara, Galimberti, Daniela, Scarpini, Elio, Saresella, Marina, Clerici, Mario·2023·International Journal of Molecular Sciences
DOI 10.3390/ijms24108626PMC PMC10218378
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Abstract

Alzheimer’s Disease is the most common form of dementia; its key pathological findings include the deposition of extracellular-neurotoxic-plaques composed of amyloid-beta (Ab). AD-pathogenesis involves mechanisms that operate outside the brain, and new researches indicate that peripheral inflammation is an early event in the disease. Herein, we focus on a receptor known as triggering-receptor-expressed-on-myeloid-cells2 (TREM2), which promotes the optimal immune cells function required to attenuate AD-progression and is, therefore, a potential target as peripheral diagnostic and prognostic-biomarker for Alzheimer’s Disease. The objective of this exploratory study was to analyze: (1) soluble-TREM2 (sTREM2) plasma and cerebrospinal fluid concentration, (2) TREM2-mRNA, (3) the percentage of TREM2-expressing monocytes, and (4) the concentration of miR-146a-5p and miR-34a-5p suspected to influence TREM2 transcription. Experiments were performed on PBMC collected by 15AD patients and 12age-matched healthy controls that were unstimulated or treated in inflammatory (LPS) conditions and Ab42 for 24 h; Aβ42-phagocytosis was also analyzed by AMNIS FlowSight. Results although preliminary, due to limitations by the small sample-size, showed that in AD compared to HC: TREM2 expressing monocytes were reduced, plasma sTREM2 concentration and TREM2-mRNA were significantly upregulated and Ab42-phagocytosis was diminished (for all p < 0.05). miR-34a-5p expression was reduced (p = 0.02) as well in PBMC of AD, and miR-146 was only observed in AD cells (p = 0.0001).

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Authors
La Rosa, F., Agostini, S., Piancone, F., Marventano, I., Hernis, A., Fenoglio, C., Galimberti, D., Scarpini, E., Saresella, M., & Clerici, M.
Affiliations
  • IRCCS Fondazione Don Carlo Gnocchi, 20147 Milan, Italy
  • Department of Pathophysiology and Transplantation, University of Milan, 20100 Milan, Italy
  • Fondazione Ca’ Granda, IRCCS Ospedale Maggiore Policlinico, 20122 Milan, Italy
ORCID
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2023-05-11
Volume
24
Issue
10
Pages
8626
ISSN
1422-0067
DOI
10.3390/ijms24108626
PMC
PMC10218378
Cited by
50
References
25
Language
en
Licence
creativecommons.org/licenses/by/4.0/ (vor)
Funders
  • Ricerca Corrente, Italian Ministry of Health
  • Fondazione Alessandro
  • Vincenzo Negroni Prati Morosini
  • Fondazione Romeo
  • Enrica Invernizzi

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