Search

Objective – Glycogen synthase kinase-3β (GSK-3β) and cyclin-dependent kinase 5 (CDK5) have been implicated as two major protein kinases involved in the abnormal hyperphosphorylation of tau in Alzheimer’s disease (AD) brain, and the development of neurofibrillary tangles. CDK5 regulatory subunit 1 (CDK5R1) encodes for p35, a protein required for activation of CDK5. As both CDK5R1 and GSK-3β genes are related to phosphorylation of tau, we examined the combined contribution of these genes to the susceptibility for AD. Methods – In a case–control study in 283 AD patients and 263 healthy controls, we examined the combined effects between CDK5R1 (3′-UTR, rs735555) and GSK-3β (−50, rs334558) polymorphisms on susceptibility to AD. Results – Subjects carrying both the CDK5R1 (3′-UTR, rs735555) AA genotype and the GSK-3β (−50, rs334558) CC genotype had a 12.5-fold decrease in AD risk (adjusted by age, sex and APOE status OR = 0.08, 95% CI = 0.01–0.76, P = 0.03), suggesting synergistic effects (epistasis) between both genes. Conclusion – These data support a role for tau phosphorylation regulating genes in risk for AD.

Mateo I, Infante J, Sanchez-Juan P, Garcia-Gorostiaga I, Rodriguez-Rodriguez E, Vazquez-Higuera JL, Berciano J, Combarros O. Serum heme oxygenase-1 levels are increased in Parkinson’s disease but not in Alzheimer’s disease. Acta Neurol Scand: 2010: 121: 136–138. © 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objective – Oxidative stress is implicated in Parkinson’s disease (PD) and Alzheimer’s disease (AD), and heme oxygenase-1 (HO-1) is a potent antioxidant overexpressed in PD substantia nigra and AD cerebral cortex and hippocampus, indicating a possible up-regulation of antioxidant defenses in both neurodegenerative diseases. The role of HO-1 in peripheral blood of PD and AD patients remains unresolved. Methods – We measured serum HO-1 levels in 107 patients with PD, 105 patients with AD, 104 controls for PD and 120 controls for AD. Results – The median serum concentration of HO-1 was significantly higher in PD patients (2.04 ng/ml) compared with that of PD controls (1.69 ng/ml, P = 0.016), with PD patients predominating over controls in the upper tertile of serum HO-1 levels, whereas there was more PD controls than PD patients in the lower tertile (P = 0.006). Median serum levels of HO-1 did not differ significantly between AD patients and AD controls. Conclusion – The increase of serum HO-1 levels in PD patients could indicate a systemic antioxidant reaction related to a chronic oxidative stress state in PD brain.

Objective – As vascular endothelial growth factor (VEGF) determines important neurotrophic and neuroprotective actions, we postulated serum VEGF levels could be abnormally low in patients with Alzheimer's disease (AD). Methods – We measured serum VEGF levels (VEGF165 isoform by ELISA) in 51 patients with AD by National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorder Association criteria and compared with 66 age- and gender-matched non-demented controls. Patients with AD were stratified into levels of dementia severity by the Clinical Dementia Rating scale. Serum VEGF levels were stratified into upper (>309 pg/ml), middle (207–309 pg/ml), and lower (

Background – Variants in genes encoding enzymes involved in production, aggregation or degradation of β-amyloid are potential risk factors for sporadic Alzheimer’s disease (AD). Methods – Meta-analyses on AD association with BACE1 exon 5, BACE1 intron 5, FE65 intron 13, CYP46 intron 2, α1-antichymotrypsine Ala17Thr, bleomycin hydrolase I443V, lectin-like oxidized low-density lipoprotein receptor (OLR1) 3′-UTR (+1071) and (+1073), and very-low-density lipoprotein receptor (VLDLR) 5′-UTR (CGG-repeat) polymorphisms. Results – In BACE1 exon 5, genotype CC+CT acts as a protective factor in Apolipoprotein E (ApoE) e4 carriers [odds ratio (OR) = 0.57; 95% confidence interval (CI): 0.38–0.88], and as a risk factor in ApoE e4 non-carriers (OR = 1.33; 95% CI: 1.00–1.78). OLR1 3′-UTR (+1073) allele C is associated with increased risk (OR = 1.23; 95% CI: 1.01–1.50). VLDLR 5′-UTR genotype 2 is associated with increased risk (OR = 1.70; 95% CI: 1.09–2.63) in the Asian population and is protective (OR = 0.48; 95% CI: 0.26–0.86) in the non-Asian population. Other studied polymorphisms are not associated with AD. Conclusions – The overall impact on AD risk of the genes for which meta-analyses are now available is rather limited. Additional meta-analyses of other different genes encoding for Aβ production, aggregation and degradation mediators might help in determining the risk profile for AD.