Vilas Menon

Oct 15, 2024 | nature.com | John Tuddenham |Anthony Khairallah |Bradley T. Hyman |Sarah C. Hopp |Naomi Habib |Hans-Ulrich Klein | +5 more

AbstractHuman microglia play a pivotal role in neurological diseases, but we still have an incomplete understanding of microglial heterogeneity, which limits the development of targeted therapies directly modulating their state or function. Here, we use single-cell RNA sequencing to profile 215,680 live human microglia from 74 donors across diverse neurological diseases and CNS regions.

May 14, 2024 | nature.com | Shahram Oveisgharan |Lei Yu |Vladislav A. Petyuk |Ricardo Assunção Vialle |Vilas Menon

AbstractAccumulation of amyloid-β (Aβ) and tau tangles are hallmarks of Alzheimer’s disease. Aβ is extracellular while tau tangles are typically intracellular, and it is unknown how these two proteinopathies are connected. Here, we use data of 1206 elders and test that RNA expression levels of GPER1, a transmembrane protein, modify the association of Aβ with tau tangles. GPER1 RNA expression is related to more tau tangles (p = 0.001).

Mar 21, 2024 | nature.com | Lu Zeng |Bernard Ng |Hyo Jung Lee |Atlas Khan |Badri Vardarajan |Krzysztof Kiryluk | +9 more

AbstractThe relationship between genetic variation and gene expression in brain cell types and subtypes remains understudied. Here, we generated single-nucleus RNA sequencing data from the neocortex of 424 individuals of advanced age; we assessed the effect of genetic variants on RNA expression in cis (cis-expression quantitative trait loci) for seven cell types and 64 cell subtypes using 1.5 million transcriptomes.

Nov 30, 2023 | nature.com | Hyun-Sik Yang |Vilas Menon |Hilary Finucane |Hans-Ulrich Klein |Lori B. Chibnik |Julie Schneider | +1 more

AbstractMany of the Alzheimer’s disease (AD) risk genes are specifically expressed in microglia and astrocytes, but how and when the genetic risk localizing to these cell types contributes to AD pathophysiology remains unclear. Here, we derive cell-type-specific AD polygenic risk scores (ADPRS) from two extensively characterized datasets and uncover the impact of cell-type-specific genetic risk on AD endophenotypes.

Jun 19, 2023 | nature.com | Dylan Lee |Feng Zhang |Esti Yeger-Lotem |Hyun-Sik Yang |Aviv Regev |Vilas Menon | +1 more

AbstractThe role of different cell types and their interactions in Alzheimer’s disease (AD) is a complex and open question. Here, we pursued this question by assembling a high-resolution cellular map of the aging frontal cortex using single-nucleus RNA sequencing of 24 individuals with a range of clinicopathologic characteristics.