Single-Cell Peripheral Immunoprofiling of Lewy Body Disease in a Multi-site Cohort

Thanaphong Phongpreecha; Kavita Mathi; Brenna Cholerton; Eddie J. Fox; Natalia Sigal; Camilo A. Espinosa; S. Momsen Reincke; Philip Chung; Ling-Jen Hwang; Chandresh R. Gajera; Eloïse Berson; Amalia Perna; Feng Xie; Chi-Hung Shu; Debapriya Hazra; Divya Channappa; Jeffrey Dunn; Lucas B. Kipp; Kathleen L. Poston; Kathleen S. Montine; Holden Terry Maecker; Nima Aghaeepour; Thomas Jude Montine

doi:10.1101/2024.01.30.578082

NeurosciencebioRxivJan 30, 2024

Preprint

Single-Cell Peripheral Immunoprofiling of Lewy Body Disease in a Multi-site Cohort

Thanaphong Phongpreecha iD, Kavita Mathi, Brenna Cholerton iD, Eddie J. Fox, Natalia Sigal iD, Camilo A. Espinosa iD, S. Momsen Reincke iD, Philip Chung iD, Ling-Jen Hwang, Chandresh R. Gajera iD, Eloïse Berson iD, Amalia Perna iD, Feng Xie iD, Chi-Hung Shu iD, Debapriya Hazra iD, Divya Channappa, Jeffrey Dunn iD, Lucas B. Kipp iD, Kathleen L. Poston iD, Kathleen S. Montine iD, Holden Terry Maecker iD, Nima Aghaeepour iD, Thomas Jude Montine iD

Abstract

Studies implicated peripheral organs involvement in the development of Lewy body disease (LBD), a spectrum of neurodegenerative diagnoses that include Parkinsons Disease (PD) without or with dementia (PDD) and dementia with Lewy bodies (DLB). This study characterized peripheral immune responses unique to LBD at single-cell resolution. Peripheral mononuclear cell (PBMC) samples were collected from sites across the U.S. The diagnosis groups comprise healthy controls (HC, n=164), LBD (n=132), Alzheimers disease dementia (ADD, n=98), other neurodegenerative disease controls (NDC, n=21), and immune disease controls (IDC, n=14). PBMCs were activated with three stimulants, stained by surface and intracellular signal markers, and analyzed by flow cytometry, generating 1,184 immune features. Our model classified LBD from HC with an AUROC of 0.90{+/-}0.06. The same model distinguished LBD from ADD, NDC, IDC, or other common conditions associated with LBD. Model predictions were driven by pPLC{gamma}2, p38, and pSTAT5 signals from specific cell populations and activations.

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