Serum Sirtuin-1, HMGB1-TLR4, NF-KB and IL-6 levels in Alzheimer's: The Relation Between Neuroinflammatory Pathway and Severity of Dementia.

Alzheimer's disease (AD), which affects the world's aging population, is a progressive neurodegenerative disease requiring markers or tools to accurately and easily diagnose and monitor the process accurately and easily. OBJECTIVE: In this study, serum Sirtuin-1(SIRT-1), High Mobility Group Box 1 (HMGB1), Toll-Like Receptor-4 (TLR4), Nuclear Factor Kappa B (NF-kB), Interleukine-6 (IL-6), Amyloid ßeta-42 (Aß-42), and p-tau181 levels in patients diagnosed with AD according to NINCS-ADRA criteria were studied. We investigated the inflammatory pathways that lead to progressive neuronal loss and highlight their possible relationship with dementia severity in the systemic circulation. METHODS: Patients over 60 years of age were grouped according to their Standard Mini Mental Test results, MRI, and/or Fludeoxyglucose positron emission tomography or according to their CT findings as Control n:20; AD n:32; Vascular Dementia (VD) n:17; AD + VD; n=21. Complete blood count, Glucose, Vitamin B12, Folic Acid, Enzymes, Urea, Creatinine, Electrolytes, Bilirubin, and Thyroid Function tests were evaluated. ELISA was used for the analysis of serum SIRT1, HMGB1, TLR4, NF-kB, IL-6, Aß-42, and p-tau181 levels. RESULTS: Levels of serum Aß-42, SIRT1, HMGB1, and IL-6 were significantly higher (p˂0.001, p<0.01, p<0.001, and p<0.001, respectively), and TLR4 levels were significantly lower (p˂0.001) in the dementia group than in the control group. No significant difference was observed between dementia and control groups for serum NF-kB and p-tau181 levels. CONCLUSION: Our results show that the levels of the Aß42, SIRT 1, HMGB1, and TLR4 pathways are altered in AD and VD. SIRT 1 activity plays an important role in the inflammatory pathway of dementia development, particularly in AD.

Four Turkish families with hyperekplexia: A missense mutation and the exon 1-7 deletion in the GLRA1 gene.

BACKGROUND: Hyperekplexia is a disease that progresses with excessive startle attacks and is included in the differential diagnosis of epilepsy and many movement disorders. METHODS: The WES results were validated in available family members by Sanger sequencing, or in the case of deletion, PCR followed by agarose gel electrophoresis was performed. RESULTS: WES analysis revealed the previously reported homozygous c.277C>T p.Arg93Trp variant in the GLRA1 gene (ENST00000455880.2) in Family 1. In all other three families, the previously reported homozygous deletion of exons 1-7 of the GLRA1 gene was identified using CNV analysis based on the WES data. CONCLUSIONS: The homozygous exon1-7 deletion has been described several times in different populations and may be a founder mutation in the Kurdish people in Turkey. The family with Arg93Trp variant stems from the Black Sea region of Turkey where close consanguinity is common. These analyses are important to provide genetic counseling to families and for a better understanding of the pathophysiology of the disease.

ADCY5 gene mutation: a case report.

BACKGROUND: ADCY5 mutation is a clinical condition that has been described in limited numbers in the literature, causing hyperkinetic movement disorder, and may be sporadic or familial. PATIENT DESCRIPTION: This report looks at the involuntary movements that started early in life in a 5-year-old girl. RESULTS: Patient's electroensephalogram and cranial magnetic resonance imaging were normal. Metabolic scans were normal. ADCY5 mutation was found in whole exome sequencing of the patient who did not have a similar family history. CONCLUSION: Some features such as the worsening of involuntary movements after sleep and the presence of hypotonia in our patient suggested this mutation. Our patient is resistant to more than one drug. With this report, we aimed to pave the way for better understanding of the gene and the discovery of different treatment options.