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1.  Co-morbidities increase the risk of disability pension among MS patients: a population-based nationwide cohort study 
BMC Neurology  2014;14:117.
Background
Multiple sclerosis (MS) is a chronic and often disabling disease. In 2005, 62% of the MS patients in Sweden aged 16–65 years were on disability pension. The objective of this study is to investigate whether the presence of common co-morbidities increase MS patients’ risk for disability pension.
Methods
This population-based cohort study included 4 519 MS patients and 4 972 174 non-MS patients who in 2005 were aged 17–64 years, lived in Sweden, and were not on disability pension. Patients with MS were identified in the nationwide in- and outpatient registers, while four different registers were used to construct three sets of measures of musculoskeletal, mental, and cardiovascular disorders. Time-dependent proportional hazard models with a five-year follow up were performed, adjusting for socio-demographic factors.
Results
All studied disorders were elevated among MS patients, regardless of type of measure used. MS patients with mental disorders had a higher risk for disability pension than MS patients with no such co-morbidities. Moreover, mental disorders had a synergistic influence on MS patients’ risk for disability pension. These findings were also confirmed when conducting sensitivity analyses. Musculoskeletal disorders appeared to increase MS patients’ risk for disability pension. The results with regard to musculoskeletal disorders’ synergistic influence on disability pension were however inconclusive. Cardiovascular co-morbidity had no significant influence on MS-patients’ risk for disability pension.
Conclusions
Co-morbidities, especially mental disorders, significantly contribute to MS patients’ risk of disability pension, a finding of relevance for MS management and treatment.
doi:10.1186/1471-2377-14-117
PMCID: PMC4055212  PMID: 24894415
Multiple sclerosis; Co-morbidity; Disability pension; Sick leave; Synergistic effects; Insurance medicine
2.  Novel Progranulin Mutation Detected in 2 Patients With FTLD 
Frontotemporal lobar degeneration (FTLD) with ubiquitin-positive, tau-negative inclusions, and linkage to chromosome 17 was recently found to be caused by mutations in the progranulin (PGRN) gene. In this study, we screened a group of 51 FTLD patients for PGRN mutations and identified a novel exon 6 splice donor site deletion (IVS6+5_8delGTGA) in 2 unrelated patients. This mutation displayed an altered splicing pattern generating 2 aberrant transcripts and causing frameshifts of the coding sequence, premature termination codons, and a near absence of PGRN mRNA from the mutated alleles most likely through nonsense-mediated decay. The subsequent PGRN haploinsufficiency is consistent with previously described PGRN mutations. We present a molecular characterization of the IVS6+5_8delGTGA mutation and also describe clinical and neuropathologic features from the 2 patients carrying this PGRN mutation. From the screening of these 51 FTLD patients, we could also identify the earlier reported mutation Gln130fs, and several coding sequence variants that are most likely nonpathogenic.
doi:10.1097/WAD.0b013e3181fbc22c
PMCID: PMC3710288  PMID: 20975516
frontotemporal lobar degeneration; frontotemporal dementia; progranulin; ubiquitin; TDP-43
3.  CALHM1 P86L polymorphism does not alter amyloid-β or tau in cerebrospinal fluid 
Neuroscience letters  2009;469(2):265-267.
Recently, the P86L alteration in CALHM1 (calcium homeostasis modulator-1) was reported to be associated with Alzheimer’s disease (AD). Moreover, the risk allele increased amyloid-β (Aβ) levels in conditioned media from cultured cells. Therefore, we hypothesized that CALHM1 P86L may modulate Aβ or tau levels in cerebrospinal fluid (CSF). Nearly 200 individuals with AD or other cognitive disorders were included for CSF analysis and CALHM1 genotyping. No significant differences in CSF levels of Aβ42, tau or phospho-tau were found across the various CALHM1 genotypes. In conclusion, we found no evidence that CALHM1 P86L is associated with altered CSF levels of the investigated AD biomarkers.
doi:10.1016/j.neulet.2009.12.011
PMCID: PMC2860374  PMID: 20005921
CALHM1; Calcium homeostasis modulator-1; Amyloid-β; Alzheimer’s disease; Cerebrospinal fluid; Biomarker; Total tau; Phospho-tau; Genotyping SNP
4.  Further analysis of previously implicated linkage regions for Alzheimer's disease in affected relative pairs 
BMC Medical Genetics  2009;10:122.
Background
Genome-wide linkage studies for Alzheimer's disease have implicated several chromosomal regions as potential loci for susceptibility genes.
Methods
In the present study, we have combined a selection of affected relative pairs (ARPs) from the UK and the USA included in a previous linkage study by Myers et al. (Am J Med Genet, 2002), with ARPs from Sweden and Washington University. In this total sample collection of 397 ARPs, we have analyzed linkage to chromosomes 1, 9, 10, 12, 19 and 21, implicated in the previous scan.
Results
The analysis revealed that linkage to chromosome 19q13 close to the APOE locus increased considerably as compared to the earlier scan. However, linkage to chromosome 10q21, which provided the strongest linkage in the previous scan could not be detected.
Conclusion
The present investigation provides yet further evidence that 19q13 is the only chromosomal region consistently linked to Alzheimer's disease.
doi:10.1186/1471-2350-10-122
PMCID: PMC2791756  PMID: 19951422
5.  Does APOE Explain the Linkage of Alzheimer’s Disease to Chromosome 19q13? 
We have studied the impact of the apolipoprotein E gene (APOE) on the chromosome 19 linkage peak from an analysis of sib-pairs affected by Alzheimer’s disease. We genotyped 417 affected sib-pairs (ASPs) collected in Sweden and Norway (SWE), the UK and the USA for 10 microsatellite markers on chromosome 19. The highest Zlr (3.28, chromosome-wide P-value 0.036) from the multipoint linkage analysis was located approximately 1 Mb from APOE, at marker D19S178. The linkage to chromosome 19 was well explained by APOE in the whole sample as well as in the UK and USA subsamples, as identity by descent (IBD) increased with the number of ε4 alleles in ASPs. There was a suggestion from the SWE subsample that linkage was higher than would be expected from APOE alone, although the test for this did not reach formal statistical significance. There was also a significant age at onset (aao) effect on linkage to chromosome 19q13 in the whole sample, which manifested itself as increased IBD sharing in relative pairs with lower mean aao. This effect was partially, although not completely, explained by APOE. The aao effect varied considerably between the different subsamples, with most of the effect coming from the UK sample. The other samples showed smaller effects in the same direction, but these were not significant.
doi:10.1002/ajmg.b.30681
PMCID: PMC2726752  PMID: 18161859
Alzheimer’s disease; APOE; linkage; age at onset; apolipoprotein E

Results 1-5 (5)