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iPS-derived MIcroglia and Neuroinflammation in Dementia

iPS-derived MIcroglia and Neuroinflammation in Dementia

Objective

Alzheimer’s disease (AD) is an irreversible neurodegenerative condition affecting 50 million people worldwide. To date, no disease modifying therapy for AD is available. Neuroinflammation is emerging as an important component of the disease. A recent GWAS analysis identified a rare protective coding mutation (P522A) in the PLCG2 (Phospholipase C Gamma 2) gene that is associated with AD. Interestingly, the gene encodes a transmembrane signaling enzyme that is highly enriched in microglia. The major aim of the proposal revolves around the functional characterization of the P522A mutation in microglia. To that aim, using an array of biochemical, imaging, functional, and transcriptomic assays, we will investigate human microglia generated from control- and AD patient-derived induced pluripotent stem cells (iPSCs). iPSCs will be gene-edited to generate P522A mutated isogenic cell lines. The proposal aims at identifying novel therapeutic targets and, in line with the objectives of the H2020 Framework Programme, explores new grounds in the molecular underpinnings of AD. The use of cutting-edge and innovative approaches (CRISPR/Cas9 gene editing, iPSC reprogramming, RNA-Seq analysis, high-throughput screening, and subcellular calcium imaging) provides a novel experimental model that is closer to the pathological processes of the AD brain and bypasses the limitations and shortcomings of preclinical AD animal models.
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Coordinator

UNIVERSITA DEGLI STUDI GABRIELE D'ANNUNZIO DI CHIETI-PESCARA

Address

Via Dei Vestini 31
66013 Chieti

Italy

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 269 002,56

Partners (1)

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THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

Project information

Grant agreement ID: 841665

Status

Grant agreement signed

  • Start date

    1 January 2020

  • End date

    31 December 2022

Funded under:

H2020-EU.1.3.2.

  • Overall budget:

    € 269 002,56

  • EU contribution

    € 269 002,56

Coordinated by:

UNIVERSITA DEGLI STUDI GABRIELE D'ANNUNZIO DI CHIETI-PESCARA

Italy