Alzheimer's disease CSF biomarkers correlate with early pathology and alterations in neuronal and glial gene expression.

Introduction: Normal pressure hydrocephalus (NPH) patients undergoing cortical shunting frequently show early 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 CSF biomarkers for AD-related 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.

ZCCHC17 Modulates Neuronal RNA Splicing and Supports Cognitive Resilience in Alzheimer's Disease.

ZCCHC17 is a putative master regulator of synaptic gene dysfunction in Alzheimer's disease (AD), and ZCCHC17 protein declines early in AD brain tissue, before significant gliosis or neuronal loss. Here, we investigate the function of ZCCHC17 and its role in AD pathogenesis using data from human autopsy tissue (consisting of males and females) and female human cell lines. Co-immunoprecipitation (co-IP) of ZCCHC17 followed by mass spectrometry analysis in human iPSC-derived neurons reveals that ZCCHC17's binding partners are enriched for RNA-splicing proteins.

ZCCHC17 modulates neuronal RNA splicing and supports cognitive resilience in Alzheimer's disease.

ZCCHC17 is a putative master regulator of synaptic gene dysfunction in Alzheimer's Disease (AD), and ZCCHC17 protein declines early in AD brain tissue, before significant gliosis or neuronal loss. Here, we investigate the function of ZCCHC17 and its role in AD pathogenesis. Co-immunoprecipitation of ZCCHC17 followed by mass spectrometry analysis in human iPSC-derived neurons reveals that ZCCHC17's binding partners are enriched for RNA splicing proteins.

Misexpression of genes lacking CpG islands drives degenerative changes during aging.

Cellular aging is characterized by disruption of the nuclear lamina and its associated heterochromatin. How these structural changes within the nucleus contribute to age-related degeneration of the organism is unclear. Genes lacking CpG islands (CGI genes) generally associate with heterochromatin when they are inactive.

An immune response characterizes early Alzheimer's disease pathology and subjective cognitive impairment in hydrocephalus biopsies.

Early Alzheimer's disease (AD) pathology can be found in cortical biopsies taken during shunt placement for Normal Pressure Hydrocephalus. This represents an opportunity to study early AD pathology in living patients. Here we report RNA-seq data on 106 cortical biopsies from this patient population.