Asian Science Citation Index is committed to provide an authoritative, trusted and significant information by the coverage of the most important and influential journals to meet the needs of the global scientific community.  
ASCI Database
308-Lasani Town,
Sargodha Road,
Faisalabad, Pakistan
Fax: +92-41-8815544
Contact Via Web
Suggest a Journal
 
Articles by J. B Leverenz
Total Records ( 2 ) for J. B Leverenz
  Z Hong , M Shi , K. A Chung , J. F Quinn , E. R Peskind , D Galasko , J Jankovic , C. P Zabetian , J. B Leverenz , G Baird , T. J Montine , A. M Hancock , H Hwang , C Pan , J Bradner , U. J Kang , P. H Jensen and J. Zhang
 

Biomarkers are urgently needed for the diagnosis and monitoring of disease progression in Parkinson’s disease. Both DJ-1 and -synuclein, two proteins critically involved in Parkinson’s disease pathogenesis, have been tested as disease biomarkers in several recent studies with inconsistent results. These have been largely due to variation in the protein species detected by different antibodies, limited numbers of patients in some studies, or inadequate control of several important variables. In this study, the nature of DJ-1 and -synuclein in human cerebrospinal fluid was studied by a combination of western blotting, gel filtration and mass spectrometry. Sensitive and quantitative Luminex assays detecting most, if not all, species of DJ-1 and -synuclein in human cerebrospinal fluid were established. Cerebrospinal fluid concentrations of DJ-1 and -synuclein from 117 patients with Parkinson’s disease, 132 healthy individuals and 50 patients with Alzheimer’s disease were analysed using newly developed, highly sensitive Luminex technology while controlling for several major confounders. A total of 299 individuals and 389 samples were analysed. The results showed that cerebrospinal fluid DJ-1 and -synuclein levels were dependent on age and influenced by the extent of blood contamination in cerebrospinal fluid. Both DJ-1 and -synuclein levels were decreased in Parkinson’s patients versus controls or Alzheimer’s patients when blood contamination was controlled for. In the population aged ≥65 years, when cut-off values of 40 and 0.5 ng/ml were chosen for DJ-1 and -synuclein, respectively, the sensitivity and specificity for patients with Parkinson’s disease versus controls were 90 and 70% for DJ-1, and 92 and 58% for -synuclein. A combination of the two markers did not enhance the test performance. There was no association between DJ-1 or -synuclein and the severity of Parkinson’s disease. Taken together, this represents the largest scale study for DJ-1 or -synuclein in human cerebrospinal fluid so far, while using newly established sensitive Luminex assays, with controls for multiple variables. We have demonstrated that total DJ-1 and -synuclein in human cerebrospinal fluid are helpful diagnostic markers for Parkinson’s disease, if variables such as blood contamination and age are taken into consideration.

  S Jayadev , J. B Leverenz , E Steinbart , J Stahl , W Klunk , C. E Yu and T. D. Bird
 

Mutations in presenilin 2 are rare causes of early onset familial Alzheimer’s disease. Eighteen presenilin 2 mutations have been reported, although not all have been confirmed pathogenic. Much remains to be learned about the range of phenotypes associated with these mutations. We have analysed our unique collection of 146 affected cases in 11 Volga German families, 101 who are likely to have the same N141I mutation in presenilin 2 (54 genotyped confirmed). We have also assessed the detailed neuropathologic findings in 18 autopsies from these families and reviewed the world’s literature on other presenilin 2 mutations; presenting a novel mutation that is predicted to lead to a premature truncation codon. Seven presenilin 2 mutations reported in the literature have strong evidence for pathogenicity whereas others may be benign polymorphisms. One hundred and one affected persons, with sufficient historical information from the Volga German pedigrees (N141I mutation), had a mean onset age of 53.7 years ± 7.8 (range 39–75) and mean age at death of 64.2 years ± 9.8 (range 43–88). These figures overlap with and generally fall between the results from the subjects in our centre who have late onset familial Alzheimer’s disease or mutations in presenilin 1. Seizures were noted in 20 (30%) of 64 subjects with detailed medical records. Two mutation carriers lived beyond age 80 without developing dementia, representing uncommon examples of decreased penetrance. Two persons had severe amyloid angiopathy and haemorrhagic stroke. Eighteen cases had detailed histopathology available and analysed at our institution. Braak stage was five or six, amyloid angiopathy and neuritic plaques were common and more than 75% had Lewy bodies in the amygdala. TAR DNA-binding protein-43 inclusions were uncommon. In addition, a 58-year-old female with a 2 year course of cognitive decline and no family history of dementia has abnormal fludeoxyglucose-positron emission tomography imaging and a novel 2 base pair deletion in presenilin 2 at nucleotide 342/343, predicted to produce a frame-shift and premature termination. We conclude that mutations in presenilin 2 are rare with only seven being well documented in the literature. The best studied N141I mutation produces an Alzheimer’s disease phenotype with a wide range of onset ages overlapping both early and late onset Alzheimer’s disease, often associated with seizures, high penetrance and typical Alzheimer’s disease neuropathology. A novel premature termination mutation supports loss of function or haploinsufficiency as pathogenic mechanisms in presenilin 2 associated Alzheimer’s disease.

 
 
 
Copyright   |   Desclaimer   |    Privacy Policy   |   Browsers   |   Accessibility