The features analysis of hemoglobin expression on visual information transmission pathway in early stage of Alzheimer's disease

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder characterized primarily by cognitive impairment. The motivation of this paper is to explore the impact of the visual information transmission pathway (V-H pathway) on AD, and the following feature were observed: Hemoglobin expression on the V-H pathway becomes dysregulated as AD occurs so as to the pathway becomes dysfunctional. According to the feature, the following conclusion was proposed: As AD occurs, abnormal tau proteins penetrate bloodstream and arrive at the brain regions of the pathway. Then the tau proteins or other toxic substances attack hemoglobin molecules. Under the attack, hemoglobin expression becomes more dysregulated. The dysfunction of V-H pathway has an impact on early symptoms of AD, such as spatial recognition disorder and face recognition disorder.

Keywords: Alzheimer’s disease; Hemoglobin; Visual information transmission pathway.

Figure 1

The illustration of the Visual–Hippocampal pathway. Information received by the eyes is processed through two visual pathways after reaching the occipital lobe. The blue portion represents the dorsal visual pathway passing through the middle temporal region, while the orange portion represents the ventral visual pathway passing through the inferior temporal region. After visual processing, the majority of information is transmitted to the parahippocampal gyrus and further relayed to the hippocampus.

Figure 2

Flowchart of the Visual–Hippocampal pathway. Stage 1 represents the visual processing stage, Stage 2 involves the transmission of visual information to the parahippocampal gyrus, and Stage 3 illustrates the relay from the parahippocampal gyrus to the hippocampus.

Figure 3

The framework of study.

Figure 4

The identification of AD genes using the method of fold change. The genes of hemoglobin subunits are included in the intersection.

Figure 5

The identification of AD genes using expression difference. The genes of hemoglobin subunits are included in the intersection.

Figure 6

PPI Network. Hemoglobin subunits form a minimized closed loop.

Figure 7

Expression levels of hemoglobin subunits on V–H Pathway. The expression levels exhibited a decreasing trend with the onset of AD.

Figure 8

The trend of entropy of the hemoglobin system in the V–H pathway. At early AD stage, brain regions MTG and HC hold increased entropy and hemoglobin expression becomes more disordered.

Figure 9

The correlation between different brain regions along the V–H pathway. The correlation MTG–PHG becomes weak significantly, the information transmission becomes weak, where the information is responsible for spatial orientation. So, the earliest symptom is spatial orientation disorder, and the symptom is high risk. At early stage, PHG–HC becomes weak significantly, and saving information becomes weak. So, the two symptoms are high-risk spatial orientation disorder and object recognition disorder.

Figure 10

The relationship between NFTs and the size correlation of hemoglobin expression at two neighbor regions.

Figure 11

The relationship between NFTs and the proportion correlation of two neighbor regions.

Figure 12

The relationship between NFTs and synthesized correlation of neighbor regions.

Figure 13

The structure of tau protein (A) Distribution of alkali amino acid in a single tau. (B) Distribution of acidic amino acid in a single tau. (C) The amino acids in a single tau. (D) Tau proteins in tubulin. (E) Charge distribution (red: negative, blue: positive) (Note: Subfigures (A) and (B) are generated from website: https://www.ncbi.nlm.nih.gov/Structure/icn3d/full.html?&mmdbid=183918&bu=1&showanno=1&source=full-feature Subfigures (C–E) are generated from website: https://swissmodel.expasy.org/repository/uniprot/P10636).

Figure 14

The structure of hemoglobin. (A) Heme (iron porphyrin). (B) Heme captures oxygen. (C) Heme locates in hemoglobin. (D) Sphere of Hemoglobin. (Note: Subfigures (A, B) are downloaded from David et al. Subfigures (C, D) are downloaded from website: https://www.ncbi.nlm.nih.gov/Structure/icn3d/full.html?&mmdbid=7599&bu=1&showanno=1&source=full-feature).

Figure 15

Expression levels of hemoglobin in the FANTOM5 Human Brain CAGE Dataset. The distribution of this figure shows the following feature: Retina holds maximum hemoglobin molecules. And this suggests that, visual information transmission is associated with hemoglobin tightly.

Algorithm 1. Pearson correlation coefficient matrix.

Algorithm 2. Entropy calculation.

Figure 16

Vector Cosine Similarity and Inner Product Schematic.

Algorithm 3. Inner product, magnitude product, cosine similarity.