Elevated TMEM38B in the caudate nucleus with Alzheimer’s disease

Symptoms of normal pressure hydrocephalus (NPH) and Alzheimer's disease (AD) are similar, and it is not uncommon to misdiagnose these two conditions. Although increasing evidence supports that neuroinflammation is detectable in humans with NPH and AD alike, which resident or infiltrating cell expressing mRNA markers mediates neuroinflammation remains poorly understood. Here, we hypothesize that NPH can be differentiated from AD with mRNA biomarkers of unvaried proximity to telomeres and that CD8+ infiltrating T cells affect neurodegeneration. We examined human caudate nucleus tissue samples for the expression of transient receptor potential cation channel subfamily V member 4 (TRPV4) and transmembrane protein 38B (TMEM38B). Using genome data viewer, we then analyzed the mutability of TRPV4 and other genes in mice, rats, and humans through matching nucleotides of genes of interest with two factors associated with high mutation rate: (i) proximity to telomeres or (ii) high adenine and thymine (A+T) content. We found that TRPV4 mRNA was elevated in NPH. Unlike NPH, mRNA expressions of microtubule associated protein tau (MAPT) and TMEM38B were elevated in AD. In mice, rats, and humans, the size of TRPV4 was not varied, while in many other marker genes, the sizes were inconsistent among species. Our analyses reveal that TRPV4 gene size and mutability is conserved across three species, suggesting that TRPV4 is a reproducible biomarker of NPH in mice, rats, and humans, while TMEM38B might be expressed by multiple cell types. Two mRNA markers in the caudate nucleus distinguish AD from NPH.