Abstract
INTRODUCTION
Normal pressure hydrocephalus (NPH) patients undergoing cortical shunting frequently show early Alzheimer’s disease (AD) pathology on cortical biopsy, which is predictive of progression to clinical AD. The objective of this study was to use samples from this cohort to identify cerebrospinal fluid (CSF) biomarkers for AD-related central nervous system (CNS) pathophysiologic changes using tissue and fluids with early pathology, free of post mortem artifact.
METHODS
We analyzed Simoa, proteomic, and metabolomic CSF data from 81 patients with previously documented pathologic and transcriptomic changes.
RESULTS
AD pathology on biopsy correlates with CSF β-amyloid-42/40, neurofilament light chain (NfL), and phospho-tau-181(p-tau181)/β-amyloid-42, while several gene expression modules correlate with NfL. Proteomic analysis highlights seven core proteins that correlate with pathology and gene expression changes on biopsy, and metabolomic analysis of CSF identifies disease-relevant groups that correlate with biopsy data.
DISCUSSION
As additional biomarkers are added to AD diagnostic panels, our work provides insight into the CNS pathophysiology these markers are tracking.
Highlights
AD CSF biomarkers correlate with CNS pathology and transcriptomic changes.
Seven proteins correlate with CNS pathology and gene expression changes.
Inflammatory and neuronal gene expression changes correlate with YKL-40 and NPTXR, respectively.
CSF metabolomic analysis identifies pathways that correlate with biopsy data.
Fatty acid metabolic pathways correlate with β-amyloid pathology.
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This post is Copyright: Ali S. Ropri,
Tiffany G. Lam,
Vrinda Kalia,
Heather M. Buchanan,
Anne Marie W. Bartosch,
Elliot H. H. Youth,
Harrison Xiao,
Sophie K. Ross,
Anu Jain,
Jayanta K. Chakrabarty,
Min Suk Kang,
Deborah Boyett,
Eleonora F. Spinazzi,
Gail Iodice,
Robert A. McGovern,
Lawrence S. Honig,
Lewis M. Brown,
Gary W. Miller,
Guy M. McKhann,
Andrew F. Teich | August 28, 2024