APBB2 genetic polymorphisms are associated with severe cognitive impairment in centenarians

APBB2 gene encodes for β-amyloid precursor protein-binding family B member 2, (APBB2, FE65-like, FE65L1), an adaptor protein binding to the cytoplasmatic domain of β-amyloid precursor protein (βAPP). Over-expression of APBB2 promotes formation of β-amyloid (Aβ), the main constituent of senile plaques. Polymorphisms within APBB2 gene have been proposed as candidate risk factors for Alzheimer's disease. However, their association with longevity has never been investigated. Here we present the first attempt to analyze APBB2 polymorphisms in centenarians. We used a PCR-RFLP method to analyze two intronic nucleotide substitutions: hCV1558625 (rs17443013) and rs13133980. We found no differences in genotype or allele distribution between centenarians and young controls. After stratification of centenarians upon their cognitive performance, the APBB2 rs13133980 G allele was over-represented in centenarians with severe cognitive impairment compared to individuals without this disability. Also the hCV1558625-rs13133980 AG haplotype increased relative risk for severe cognitive impairment in centenarians. Our results support the concept of APBB2 polymorphism association with cognitive performance in the oldest age.     

Creutzfeldt-Jakob disease (CJD) of a short duration with prion protein (PrP) plaques.

We report here PrP-immunohistochemistry performed on brains from CJD cases from Poland. Only one out of five definitive CJD cases exhibited typical PrP-immunoreactive kuru-like plaques and this was case of a short duration. Thus, we confirmed the low percentage of PrP plaques in CJD of Eastern and Central European origin.     

Tubulovesicular structures in human and experimental Creutzfeldt-Jakob disease

Tubulovesicular structures (TVS) have been consistently observed in brain tissue of animals with transmissible spongiform encephalopathies such as natural and experimental scrapie, bovine spongiform encephalopathy, and experimental Creutzfeldt-Jakob disease (CJD). In this communication we demonstrate for the first time the presence of TVS in natural CJD. TVS were detected in all 3 CJD specimens. However, they were rare and were found only in one or two locations per grid. They were seen in distended pre- and postsynaptic terminals and measured approximately 35 nm in diameter, and they were smaller and of higher electron density than synaptic vesicles. Their occurrence in all types of spongiform encephalopathies irrespective of the affected host and the strain of infectious agent emphasizes their biological significance.Corresponding author.     

Laminar distribution of neuritic plaques in normal aging,Alzheimer's disease and Down's syndrome

Summary Quantitative studies of neuritic (senile) plaques in six cortical layers were carried out in brains from people with confirmed clinical and neuropathological diagnosis of senile dementia of the Alzheimer type (SDAT) and Down's syndrome (DS). The same studies were performed on brains of normal old-aged people. In Alzheimer disease (AD) and DS cases the highest numbers of neuritic plaques (NP) were observed in temporal lobe layers III and II and occipital lobe layers III, IV and II. In normal old-aged people the highest numbers of NP were found in temporal lobe III and V and in occipital lobe IV, III, and V layer. The plaque numbers in both temporal and occipital cortices of AD and DS were significantly higher than that of normal old-aged people but there was no difference between AD and DS.Supported in part by Grant Nos. AGO-4220 and HD22634 from the National Institutes of Health     

Calbindin‐1 association and Parkinson’s disease

Background and purpose: Calcium levels have been proposed to play an important role in the selective vulnerability of nigrostriatal dopaminergic neurons in Parkinson’s disease (PD). Recently, an association was reported between the calcium buffer, calbindin (rs1805874) and risk of PD in a Japanese patient–control series. Methods: We genotyped rs1805874 in four independent Caucasian patient–control series (1543 PD patients, 1771 controls). Results: There was no evidence of an association between rs1805874 and disease risk in individual populations or in the combined series (odds ratio: 1.04, 95% CI: 0.82–1.31, P = 0.74). Discussion: Our study shows there is no association between rs1805874 and risk for PD in four Caucasian populations. This suggests the effect of calbindin on PD risk displays population specificity.     

Interleukin-6 gene (-174 C/G ) and apolipoprotein E gene polymorphisms and the risk of Alzheimer disease in a Polish population

Background and purposeInflammation plays a prominent role in Alzheimer disease (AD) pathogenesis. Interleukin-6 (IL-6), a pro-inflammatory cytokine, and some genetic variations in the IL-6 gene have been reported to be associated with a risk of AD. However, the results of the conducted studies are equivocal.Material and methodsWe genotyped IL-6 (–174 C/G) and apolipoprotein E gene (APOE) common polymorphisms in a large case-controlled study in a Polish population. We included 361 patients aged ≥ 65 years with AD (mean age 75.8 ± 5.3 years, 232 females [64.3%]) and 200 controls (75.3 ± 7.4 years; 119 females [59.5%]), without any neurological deficit, cognitive complaints or history of neurological diseases. The IL-6 polymorphism was genotyped using TaqMan SNP allelic discrimination by means of an ABI 7900HT (Applied Biosystems, Foster City, CA).ResultsThe distribution of the IL-6 (–174 C/G) genotypes was similar to that in the controls (AD: C/C = 15.79%, C/G = 51.25%, G/G = 32.96% vs. controls: C/C = 21.50%, C/G = 45.50%, G/G = 33.0%, p > 0.05). Our study confirms previous reports that APOE 4 is strongly related to the risk of AD (OR = 6.17; 95% CI: 4.01–9.49). APOE status did not affect the distribution of the studied IL-6 polymorphism.ConclusionIL-6 (–174 C/G) polymorphism is not a risk factor for late onset AD in a Polish population.     

Analysis of UBQLN1 variants in a Polish Alzheimer's disease patient: control series

Late-onset Alzheimer's disease (LOAD) is the most common neurodegenerative disorder, and has a complex etiology. Recently an intronic polymorphism in the ubiquilin 1 gene (UBQLN1) and a particular haplotype was reported to be associated with LOAD. We investigated whether variants in UBQLN1 confer a risk for the disease in 407 Polish LOAD patients and 407 controls. We observed a weak association with the rs2781002 polymorphism, however, contrary to the initial reports, in our group the association was with the A allele. Risk estimation for AA versus GG genotypes showed that the AA genotype is a weak risk factor for AD (OR = 1.8, 95% CI = 1.1-3.1, p = 0.025). This effect was stronger in a group of LOAD patients without APOE4 allele. Haplotype analyses indicate that there is an increase of haplotypes with an A allele in the case group. Also, the specific haplotypes with the A allele that increase AD risk differ between the APOE4-positive and APOE4-negative pools. However, the association observed seems to be driven mostly by rare (<5%) haplotypes. Results suggest a need for additional association studies and in silico analysis of the UBQLN1 locus.