Yann Le Guen

Sep 9, 2024 | jamanetwork.com | Rachel Buckley |Michaël E. Belloy |Yann Le Guen |Ilaria Stewart

How Is the X Chromosome Involved in Alzheimer Disease? Role of the X Chromosome in Alzheimer Disease Genetics Michael E. Belloy, PhD; Yann Le Guen, PhD; Ilaria Stewart, BA; Kennedy Williams, BA; Joachim Herz, MD; Richard Sherva, PhD; Rui Zhang, MS; Victoria Merritt, PhD; Matthew S. Panizzon, PhD; Richard L. Hauger, MD; J. Michael Gaziano, MD; Mark Logue, PhD; Valerio Napolioni, PhD; Michael D.

Apr 23, 2024 | medrxiv.org | Michaël E. Belloy |Yann Le Guen |Ilaria Stewart |Joachim Herz

The authors have declared no competing interest. Funding for this study was provided by the NIH (R00AG075238, M.E.B; AG060747 and AG047366, M.D.G) and the European Union[prime]s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie (grant agreement No. 890650, Y.L.G.). JH was supported by grants from the NIH (NS108115), the Alzheimer's Association (ABA-22-970304) and the Kleberg Foundation.

Mar 27, 2024 | nature.com | Edward Wilson |Yann Le Guen |Eran Blacher |Matthew Xin |Melanie R. McReynolds |Chinyere A. Iweka

AbstractHuman genetics implicate defective myeloid responses in the development of late-onset Alzheimer disease. A decline in peripheral and brain myeloid metabolism, triggering maladaptive immune responses, is a feature of aging. The role of TREM1, a pro-inflammatory factor, in neurodegenerative diseases is unclear. Here we show that Trem1 deficiency prevents age-dependent changes in myeloid metabolism, inflammation and hippocampal memory function in mice.

Jan 31, 2024 | cell.com | Augustine Chemparathy |Yann Le Guen |Sunny Chen |Eun-Gyung Lee

The ε4 allele of apolipoprotein E (APOE) is the strongest genetic risk factor for sporadic Alzheimer’s disease (AD). Knockdown of ε4 may provide a therapeutic strategy for AD, but the effect of APOE loss of function (LoF) on AD pathogenesis is unknown. We searched for APOE LoF variants in a large cohort of controls and patients with AD and identified seven heterozygote carriers of APOE LoF variants.

Dec 6, 2023 | cell.com | Colin M. Muir |Yann Le Guen |Institut du Cerveau |Stefano E. Rensi

Highlights•Iron elevation causes inward mitochondrial Ca2+ overflow via an Fe2+-MCU interaction•In PD neurons, this Fe2+-Ca2+ signal causes Ca2+ elevation at the OMM•OMM Ca2+ levels are sensed by Miro1•Miro1-based drug screens in PD cells identify Ca2+-channel blockersSummaryDysregulated iron or Ca2+ homeostasis has been reported in Parkinson’s disease (PD) models. Here, we discover a connection between these two metals at the mitochondria.