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Cross-disorder and disease-specific pathways in dementia revealed by single-cell genomics

7 months 2 weeks ago
The development of successful therapeutics for dementias requires an understanding of their shared and distinct molecular features in the human brain. We performed single-nuclear RNA-seq and ATAC-seq in Alzheimer's disease (AD), frontotemporal dementia (FTD), and progressive supranuclear palsy (PSP), analyzing 41 participants and ∼1 million cells (RNA + ATAC) from three brain regions varying in vulnerability and pathological burden. We identify 32 shared, disease-associated cell types and 14...
Jessica E Rexach

Phosphorylation of tau at a single residue inhibits binding to the E3 ubiquitin ligase, CHIP

7 months 2 weeks ago
Microtubule-associated protein tau (MAPT/tau) accumulates in a family of neurodegenerative diseases, including Alzheimer's disease (AD). In disease, tau is aberrantly modified by post-translational modifications (PTMs), including hyper-phosphorylation. However, it is often unclear which of these PTMs contribute to tau's accumulation or what mechanisms might be involved. To explore these questions, we focus on a cleaved proteoform of tau (tauC3), which selectively accumulates in AD and was...
Cory M Nadel

Clearance and transport of amyloid beta by peripheral monocytes correlate with Alzheimer's disease progression

7 months 2 weeks ago
Impaired clearance of amyloid β (Aβ) in late-onset Alzheimer's disease (AD) affects disease progression. The role of peripheral monocytes in Aβ clearance from the central nervous system (CNS) is unclear. We use a flow cytometry assay to identify Aβ-binding monocytes in blood, validated by confocal microscopy, Western blotting, and mass spectrometry. Flow cytometry immunophenotyping and correlation with AD biomarkers are studied in 150 participants from the AIBL study. We also examine monocytes...
Xin Huang

In Science Journals

7 months 2 weeks ago
Science, Volume 385, Issue 6714, Page 1176-1178, September 2024.

Michael Funk, and
Brent Grocholski,
Aaron Shaw,
Bianca Lopez,
Ankit Walia,
Michael A. Funk,
Marc S. Lavine,
Hannah M. Isles,
Sarah H. Ross,
Ekeoma Uzogara,
Yevgeniya Nusinovich,
Caroline Ash,
Phil Szuromi,
Jake S. Yeston,
Courtney Malo, …