Analysis and Identification Genetic Effect of SARS-CoV-2 Infections to Alzheimer's Disease Patients by Integrated Bioinformatics.

BACKGROUND: COVID-19 pandemic is a global crisis which results in millions of deaths and causes long-term neurological sequelae, such as Alzheimer's disease (AD). OBJECTIVE: We aimed to explore the interaction between COVID-19 and AD by integrating bioinformatics to find the biomarkers which lead to AD occurrence and development with COVID-19 and provide early intervention. METHODS: The differential expressed genes (DEGs) were found by GSE147507 and GSE132903, respectively. The common genes between COVID-19 and AD were identified. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interactions (PPI) network analysis were carried out. Hub genes were found by cytoscape. A multivariate logistic regression model was constructed. NetworkAnalyst was used for the analysis of TF-gene interactions, TF-miRNA coregulatory network, and Protein-chemical Interactions. RESULTS: Forty common DEGs for AD and COVID-19 were found. GO and KEGG analysis indicated that the DEGs were enriched in the calcium signal pathway and other pathways. A PPI network was constructed, and 5 hub genes were identified (ITPR1, ITPR3, ITPKB, RAPGEF3, MFGE8). Four hub genes (ITPR1, ITPR3, ITPKB, RAPGEF3) which were considered as important factors in the development of AD that were affected by COVID-19 were shown by nomogram. Utilizing NetworkAnalyst, the interaction network of 4 hub genes and TF, miRNA, common AD risk genes, and known compounds is displayed, respectively. CONCLUSION: COVID-19 patients are at high risk of developing AD. Vaccination is required. Four hub genes can be considered as biomarkers for prediction and treatment of AD development caused by COVID-19. Compounds with neuroprotective effects can be used as adjuvant therapy for COVID-19 patients.

rAAV-based brain slice culture models of Alzheimer's and Parkinson's disease inclusion pathologies.

It has been challenging to produce ex vivo models of the inclusion pathologies that are hallmark pathologies of many neurodegenerative diseases. Using three-dimensional mouse brain slice cultures (BSCs), we have developed a paradigm that rapidly and robustly recapitulates mature neurofibrillary inclusion and Lewy body formation found in Alzheimer's and Parkinson's disease, respectively. This was achieved by transducing the BSCs with recombinant adeno-associated viruses (rAAVs) that express α-synuclein or variants of tau. Notably, the tauopathy BSC model enables screening of small molecule therapeutics and tracking of neurodegeneration. More generally, the rAAV BSC "toolkit" enables efficient transduction and transgene expression from neurons, microglia, astrocytes, and oligodendrocytes, alone or in combination, with transgene expression lasting for many months. These rAAV-based BSC models provide a cost-effective and facile alternative to in vivo studies, and in the future can become a widely adopted methodology to explore physiological and pathological mechanisms related to brain function and dysfunction.

Clinical Significance of Human Papillomavirus Type 16 for Breast Cancer & Adenocarcinomas of Various Internal Organs and Alzheimer's Brain with Increased ß-amyloid (1-42); Combined Use of Optimal Doses of Vitamin D3 and Taurine 3 times/day Has Significant Beneficial Effects of Anti-Cancer, Anti-Ischemic Heart, and Memory & Other Brain Problems By Significant Urinary Excretion of Viruses, Bacteria, and Toxic Metals & Substances.

Human Papillomavirus type 16 (HPV-16) has a significant role in various cancers and Alzheimer's disease. 500 breast cancer mammograms as well as 3 cases of adenocarcinomas of esophagus, stomach, colon, prostate gland, uterus, ovary that was examined had significant infection of HPV- 16 with significantly increased ß- amyloid (1-42). When a strong HPV-16 infection is found in the oral cavity, repeated exposure to the infected individual's coughing can infect others easily through saliva. Just like all of above cancer tissues, all 20 Alzheimer's cases that were examined had significantly increased HPV-16 of 1500-3000ng with markedly reduced Acetylcholine of 0.5~1.5ng and significantly increased 3- amyloid (1-42) of 7.5ng or higher. Since every cancer and Alzheimer's patient examined had significantly reduced amounts of Vitamin D3 and Taurine, the author examined the effects of Vitamin D3 and Taurine independently, or by combination. Each of optimal doses of Vitamin D3 and Taurine had significant beneficial effects that were anti-cancer, anti-cardiac ischemia, and memory loss & other brain problems, with significant excretion of HPV- 16 and bacteria such as Borrelia Burgdorferi, if it exists, through the urine, without using any anti-viral or anti-bacterial agents. However, when optimal doses of Taurine and Vitamin D3 were used together, 3 times/day, there was reduction of cancer-associated Oncogene CfosAB-2 or Integrin a5p1 with significantly high values of 200-500ng which were reduced to 0.001-0.004ng. Memory and brain function improved by increasing markedly reduced abnormal Acetylcholine of 1.5ng or less to a few hundred-2500ng with increase in DHEA. Abnormally increased P-amyloid (1-42) is markedly reduced. Ischemic heart, where there is abnormally increased Cardiac Troponin I, reduced significantly. In addition, abnormally reduced DHEA levels often increase. HPV- 16 in urine increased from an average of 100~15ng to an average of 4000ng and cancer related parameters in the urine significantly increased. Thus, the author found combined use of optimal dose of Vitamin D3 400 I.U. and optimal dose of Taurine 175mg, 3/day, was found to be one of the safest, most effective treatments for cancer, memory problems & other brain abnormality, and Ischemic heart problems, and this combination seems to improve any part of the body. One should try this method before using any other treatment, which has a potential side effect.

Anti-Viral Agents in Neurodegenerative Disorders: New Paradigm for Targeting Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disease affecting geriatric populations for which several causes have been proposed. These include a relationship with known pathogens although the exact nature of such a relationship remains uncertain. Herpes simplex virus-1 has been proposed as potential cause of AD because of its ability to form ß amyloid(Aß) and neurofibrillary tangles due to tau hyperphosphorylation and action of beta & gamma secretase on amyloid precursor protein(APP) together with genetic association with apolipoprotein-E4(ApoE-Ɛ4), which points out to latent Herpes Simplex virus-1 as an agent causing AD. There are numerous studies that linked HSV-1 with AD like anti-HSV-1 IgM antibodies, nectin-2, heme oxygenase-1, phosphorylated eukaryotic initiation factor-2A, caspase-8 and nucleus-specific alteration of raphe neurons. Various possible mechanisms by which HSV-1 might lead to development of AD such as ApoE, ß-amyloid, tau phosphorylation, inflammation and oxidative stress are also discussed. Thus, this review discusses patent information and a strong relationship between latent HSV-1 and AD and also proposes antiviral therapy for AD.