TRPV4 mRNA is elevated in the caudate nucleus with NPH but not in Alzheimer's disease

Hunter White; Ryan Webb; Ian McKnight; Kaitlyn Legg; Chan Lee; Peter H U Lee; Olivia Smith Spicer; Joon W Shim

doi:10.3389/fgene.2022.936151

TRPV4 mRNA is elevated in the caudate nucleus with NPH but not in Alzheimer's disease

Front Genet. 2022 Nov 2:13:936151. doi: 10.3389/fgene.2022.936151. eCollection 2022.

Authors

Hunter White¹, Ryan Webb¹, Ian McKnight¹, Kaitlyn Legg¹, Chan Lee², Peter H U Lee^{3

4}, Olivia Smith Spicer⁵, Joon W Shim¹

Affiliations

¹ Department of Biomedical Engineering, Marshall University, Huntington, WV, United States.
² Department of Anesthesia, Indiana University Health Arnett Hospital, Lafayette, IN, United States.
³ Department of Cardiothoracic Surgery, Southcoast Health, Fall River, MA, United States.
⁴ Department of Pathology and Laboratory Medicine, Brown University, Providence, RI, United States.
⁵ National Institute of Mental Health, National Institute of Health, Bethesda, MD, United States.

Abstract

Symptoms of normal pressure hydrocephalus (NPH) and Alzheimer's disease (AD) are somewhat similar, and it is common to misdiagnose these two conditions. Although there are fluid markers detectable in humans with NPH and AD, determining which biomarker is optimal in representing genetic characteristics consistent throughout species is poorly understood. Here, we hypothesize that NPH can be differentiated from AD with mRNA biomarkers of unvaried proximity to telomeres. We examined human caudate nucleus tissue samples for the expression of transient receptor potential cation channel subfamily V member 4 (TRPV4) and amyloid precursor protein (APP). Using the genome data viewer, we analyzed the mutability of TRPV4 and other genes in mice, rats, and humans through matching nucleotides of six genes of interest and one house keeping gene with two factors associated with high mutation rate: 1) proximity to telomeres or 2) high adenine and thymine (A + T) content. We found that TRPV4 and microtubule associated protein tau (MAPT) mRNA were elevated in NPH. In AD, mRNA expression of TRPV4 was unaltered unlike APP and other genes. In mice, rats, and humans, the nucleotide size of TRPV4 did not vary, while in other genes, the sizes were inconsistent. Proximity to telomeres in TRPV4 was <50 Mb across species. Our analyses reveal that TRPV4 gene size and mutability are conserved across three species, suggesting that TRPV4 can be a potential link in the pathophysiology of chronic hydrocephalus in aged humans (>65 years) and laboratory rodents at comparable ages.

Keywords: Alzheimer’s disease; MAPT; MRNA marker; TRPV4; normal pressure hydrocephalus.