Hereditary haemochromatosis is characterised by excessive parenchymal iron deposition, particularly in the liver. Usually hereditary haemochromatosis is not associated with neurological symptoms and iron deposition in the brain has not previously been described as a pathological phenomenon. A patient is reported with hereditary haemochromatosis and a syndrome of dementia, dysarthria, a slowly progressive gait disturbance, imbalance, muscle weakness, rigidity, bradykinesia, tremor, ataxia, and dyssynergia. The findings on MRI of a large signal decrease in the basal ganglia, consistent with excessive iron accumulation, indicate a causal relation to the symptoms. Although the neurological symptoms did not improve in our patient, hereditary haemochromatosis should be considered in the differential diagnosis of parkinsonian syndromes, because complications of iron induced organ injury may be prevented by phlebotomy.percentage saturation of transferrin and serum ferritin concentration, increased amounts of stainable iron in hepatocytes and an increased hepatic iron concentration. Most patients present with symptoms at the age of 40-50, but some may present earlier, in the second or third decade. There is a sex difference and the frequency of male to female haemochromatosis ranges from 2:1 to 18:1.2 Neurological features associated with hereditary haemochromatosis are rare. Lethargy, psychomotor retardation, fatigue, confusion, hearing loss, and polyneuropathy have been described.3To the best of our knowledge, there have been no reports of excessive iron deposition in the CNS in hereditary haemochromatosis, an otherwise well known pathological feature of the Hallervorden-Spatz syndrome and familial hypoceruloplasminaemia.We report on a patient with hereditary haemochromatosis with a parkinsonian syndrome, most likely caused by excessive iron accumulation in the basal ganglia and cerebellum.
Retinal vein occlusion (RVO) is a common retinal vascular disease. RVO may be complicated by pronounced ischemia that often leads to severe loss of visual function. The present work aimed at studying the retinal proteome of RVO complicated by ischemia. In six Danish Landrace pigs RVO was induced with argon laser in the right eye of each animal. As four retinal veins were occluded, the RVO best corresponded to a central retinal vein occlusion (CRVO). Left control eyes received a similar laser treatment without inducing occlusion. RVO and retinal ischemia were verified by angiography. The retinas were collected 15 days after RVO for proteomic analysis. RVO resulted in a downregulation of proteins involved in visual perception, including rhodopsin, transducin alpha chain, and peripherin-2. RVO also caused a downregulation of proteins involved in neurotransmitter transport, including glutamate decarboxylase 1 (GAD1), glutamate decarboxylase 2 (GAD2), and complexins 2–4. RVO lead to increased contents of proteins involved in inflammation, including interleukin-18 (IL-18), S100A12, and annexin A1 (ANXA1). Immunohistochemistry revealed a general retinal upregulation of IL-18 and ANXA1 while S100A12 was highly abundant in retinal ganglion cells in RVO. IL-18 and S100A12 are likely to be driving forces in the inflammatory response of RVO complicated by ischemia. Our findings also suggest that RVO results in compromised neurotransmission and a downregulation of proteins involved in visual perception.
Background Alzheimer's Disease (AD) is a complex and multifactorial disease and novel approaches are needed to illuminate the underlying pathology. Metabolites comprise the end-product of genes, transcripts, and protein regulations and might reflect disease pathogenesis. Blood is a common biofluid used in metabolomics; however, since extracellular vesicles (EVs) hold cell-specific biological material and can cross the blood-brain barrier, their utilization as biological material warrants further investigation. We aimed to investigate blood- and EV-derived metabolites to add insigts to the pathological mechanisms of AD. Methods Blood samples were collected from 10 AD and 10 Mild Cognitive Impairment (MCI) patients, and 10 healthy controls. EVs were enriched from plasma using 100,000× g , 1 h, 4 °C with a wash. Metabolites from serum and EVs were measured using liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR) spectroscopy. Multivariate and univariate analyses were employed to identify altered metabolites in cognitively impaired individuals. Results While no significant EV-derived metabolites were found differentiating patients from healthy individuals, six serum metabolites were found important; valine ( p = 0.001, fold change, FC = 0.8), histidine ( p = 0.001, FC = 0.9), allopurinol riboside ( p = 0.002, FC = 0.2), inosine ( p = 0.002, FC = 0.3), 4-pyridoxic acid ( p = 0.006, FC = 1.6), and guanosine ( p = 0.004, FC = 0.3). Pathway analysis revealed branched-chain amino acids, purine and histidine metabolisms to be downregulated, and vitamin B6 metabolism upregulated in patients compared to controls. Conclusion Using a combination of LC-MS and NMR methodologies we identified several altered mechanisms possibly related to AD pathology. EVs require additional optimization prior to their possible utilization as a biological material for AD-related metabolomics studies.
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