Genetic and molecular markers of cortical brain biopsy in idiopathic normal pressure Hydrocephalus: A scoping review

Abstract

Introduction

Idiopathic normal pressure hydrocephalus (iNPH) is a condition classically defined by the triad of gait disturbance, cognitive dysfunction, and urinary incontinence. While categorized under the umbrella of cognitive and gait disorders, there is no clear consensus about its molecular etiology. Brain biopsies showing the presence of specific aggregated proteins have been suggested as a potential indicator of iNPH pathophysiology. This review summates existing literature for potential iNPH biomarkers from cortical brain tissue.

Methodology

A scoping review was conducted according to PRISMA guidelines. The terms “cortical biopsy” and “normal pressure hydrocephalus” were searched on December 14th, 2023 using PubMed, EMBASE and Scopus databases. All articles were screened by two independent reviewers. Data were manually collected after quality assessment and tabulated.

Results

Twenty-one articles were included in this study. Alzheimer’s-related biomarkers were most commonly reported from brain biopsies of iNPH patients, including various types of amyloid-beta, neuritic plaques, neurofibrillary tangles, and phosphorylated tau. Amyloid-beta and phosphorylated tau were the most reported from patient cortical biopsies and attenuated levels of these biomarkers were associated with better shunt placement outcomes. Other biomarkers included several interleukins, interferons, dystrophin proteins, glial fibrillary acidic protein (GFAP), glycoproteins, and aquaporins. Increased levels of GFAP, leucine-rich-alpha-2-glycoprotein, and gamma-secretase were associated with iNPH along with decreased levels of aquaporin-4 and dystrophin protein-71.

Conclusion

Amyloid pathology is the most reported potential biomarker for iNPH patients. Second most common are markers associated with water homeostasis. Along with further exploration of other non-amyloid molecular markers, these findings could be used in the creation of animal models for further investigation.