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Acute disseminated encephalomyelitis (ADEM) is a demyelinating disease, and there are some data that link this event with various vaccinations. We report a young female admitted to the hospital with headache, fever, back pain, nausea, vomiting, and urinary retention. Two weeks prior, she received the first dose of SARS‐CoV‐2 mRNA vaccine. Brain and spinal cord magnetic resonance imaging (MRI) showed distinctive for ADEM widespread demyelinating lesions. The patient was successfully treated with methylprednisolone.

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Alzheimer’s disease (AD) is a progressive disease, with frequently observed improper biothiols turnover, homocysteine (Hcy) and glutathione (GSH). GSH protects cells from oxidative stress and may be determined by 8-oxo-2’-deoxyguanosine (8-oxo2dG) level and its repair enzyme 8-oxoguanine DNA glycosylase (OGG1). The presence of unfavorable alleles, e.g., in APOE cluster, TOMM40 or APOC1 is known to facilitate the dementia onset under oxidative stress.The aim of the study was to analyze rs1052452, rs2075650 TOMM40 polymorphisms, rs4420638 APOC1, and their correlation with Hcy, GSH, 8-oxo2dG, OGG1 levels in plasma of AD patients and controls.We recruited 230 individuals: 88 AD, 80 controls without (UC), 62 controls with (RC) positive family history of AD. The TOMM40 genotype was determined by HRM and capillary electrophoresis, while APOC1 by HRM. The concentrations of OGG1, 8-oxo2dG were determined by ELISA, whereas Hcy, GSH by HPLC/EC.We showed that over 60% of AD patients had increased Hcy levels (p<0.01 vs. UC, p<0.001 vs. RC), while GSH (p<0.01 vs. UC), 8-oxo2dG (p<0.01 vs. UC, p<0.001 vs. RC) were reduced. Minor variants: rs10524523-L, rs4420638-G, rs2075650-G were significantly overrepresented in AD. For rs4420638-G, rs2075650-G variants, the association remained significant in APOE E4 non-carriers. The misbalance of analyzed biothiols, and 8-oxo2dG, OGG1 were more pronounced in carriers of major variants: rs10524523-S/VL, rs4420638-A, rs2075650-A.We showed, for the first time, that APOC1 and TOMM40 rs2075650 polymorphisms may be independent risk factors of developing AD, whose major variants are accompanied by disruption of biothiols metabolism and inefficient removal of DNA oxidation.

Parkinson’s disease (PD) is a major public health problem. Since currently there are no reliable diagnostic tools to reveal the early steps of PD, new methods should be developed, including those searching the variations in human metabolome. Alterations in human metabolites could help to establish an earlier and more accurate diagnosis. The presented research shows a targeted metabolomics study of both of the serum and CSF from PD patients, atypical parkinsonian disorders (APDs) patients, and the control. The use of the LC-MS/MS system enabled to quantitate 144 analytes in the serum and 51 in the CSF. This information about the concentration enabled for selection of the metabolites useful for differentiation between the studied group of patients, which should be further evaluated as candidates for markers of screening and differential diagnosis of PD and APDs. Among them, the four compounds observed to be altered in both the serum and CSF seem to be the most important: tyrosine, putrescine, trans-4-hydroxyproline, and total dimethylarginine. Furthermore, we indicated the metabolic pathways potentially related to neurodegeneration processes. Our studies present evidence that the proline metabolism might be related to neurodegeneration processes underlying PD and APDs. Further studies on the proposed metabolites and founded metabolic pathways may significantly contribute to understanding the molecular background of PD and improving the diagnostics and treatment in the future.

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Current knowledge indicates that the aging process starts with subclinical changes at the molecular level. These include the accumulation of mutations, telomere attrition, and epigenetic alterations leading to genomic instability. Such defects multiply exponentially over time, resembling a "snowball effect," and eventually leading to morphological and functional deterioration of the brain, including progressive neuronal loss, reduced levels of neurotransmitters, excessive inflammation, and disrupted integrity of vessels, followed by infarction and microbleeds. Additionally, the decreasing efficiency of DNA repair mechanisms increases the susceptibility to reactive oxygen species and spontaneous mutagenesis, resulting in age-related neoplasia. Moreover, the malnutrition and malabsorption seen commonly in the elderly may cause deficiency of vitamin B 12 and folic acid, both necessary for homocysteine metabolism, and lead to vascular damage. Altogether, these lead to brain damage in old age and greatly increase the risk of developing diseases of the central nervous system, such as stroke, epilepsy, Parkinson's disease, Alzheimer's disease, and other dementias.