Journal of Alzheimer's Disease - Volume 15, issue 3

Authors: Laske, Christoph | Stellos, Konstantinos | Stransky, Elke | Seizer, Peter | Akcay, Özlem | Eschweiler, Gerhard W. | Leyhe, Thomas | Gawaz, Meinrad

Article Type: Research Article

Abstract: Alzheimer's disease (AD) is characterized by massive neuronal cell loss in the brain. Stem cell factor (SCF) is a hematopoietic growth factor (HGF) that promotes neuroprotective effects and supports neurogenesis in the brain. In the present study, we found significantly lower SCF plasma levels in 30 early AD patients (908.5 ± 181.7 pg/ml) in comparison with 30 age-matched healthy controls (1058.3 ± 221.5 pg/ml; p = 0.006). SCF plasma levels in AD patients showed a significant inverse correlation with dementia severity as measured by ADAS-Cog (r = −0.289; p = 0.037). AD patients showed significantly lower SCF levels in cerebrospinal …fluid (CSF) (131.60 ± 43.03 pg/ml) in comparison with 15 age- and gender-matched patients with other non-inflammatory neurological disease (NIND) (166.03 ± 42.5 pg/ml; p = 0.017). In addition, we found significant positive correlations between SCF and CXCL12 (also known as SDF-1) plasma levels in healthy controls (r = 0.341; p = 0.008) and between SCF and CXCL12 CSF levels in AD patients (r = 0.487; p < 0.001). In conclusion, decreased SCF plasma and CSF levels in early AD patients may contribute to a deficient hematopoietic brain support with putative pathogenic and clinical relevance. Further studies are needed to examine whether a manipulation of HGFs such as SCF could be a promising new therapeutic strategy for AD. Show more

Keywords: Alzheimer's disease, clinical relevance, neurogenesis, neuroprotection, stem cell factor

DOI: 10.3233/JAD-2008-15311

Citation: Journal of Alzheimer's Disease, vol. 15, no. 3, pp. 451-460, 2008

Authors: Connor, Donald J. | Sabbagh, Marwan N.

Article Type: Short Communication

Abstract: The Alzheimer's Disease Assessment Scale – Cognitive (ADAS-Cog) is the most commonly used primary outcome instrument in clinical trials for treatments of dementia. Variations in forms, administration procedures and scoring rules, along with rater turnover and intra-rater drift may decrease the reliability of the instrument. A survey of possible variations in the ADAS-Cog was administered to 26 volunteer raters at a clinical trials meeting. Results indicate notable protocol variations in the forms used, administration procedures, and scoring rules. Since change over time is used to determine treatment effect in clinical trials, standardizing the instrument's ambiguities and addressing common problems will …greatly increase the instrument's reliability and thereby enhance its sensitivity to treatment effects. Show more

Keywords: ADAS-Cog, administration, Alzheimer's disease, clinical trials, dementia

DOI: 10.3233/JAD-2008-15312

Citation: Journal of Alzheimer's Disease, vol. 15, no. 3, pp. 461-464, 2008

Authors: Bellinger, Frederick P. | He, Qing-Ping | Bellinger, Miyoko T. | Lin, Yanling | Raman, Arjun V. | White, Lon R. | Berry, Marla J.

Article Type: Research Article

Abstract: Selenium is known for its antioxidant properties, making selenoproteins candidate molecules for mitigation of neurological disorders in which oxidative stress has been implicated. The selenium transport protein, selenoprotein P, is essential for neuronal survival and function. We sought to determine whether selenoprotein P expression is associated with Alzheimer's disease pathology. We examined postmortem tissue from individuals with the hallmark lesions of Alzheimer's disease and individuals without these lesions. Selenoprotein P immunoreactivity was co-localized with amyloid-β plaques and neurofibrillary tangles. Dense-core and other non-diffuse amyloid-β plaques were nearly always associated with selenoprotein P immunopositive cells. Analysis of spatial distribution showed a …significant association between amyloid-β plaques and selenoprotein P. Numerous cells also exhibited immunoreactivity to selenoprotein P and intraneuronal neurofibrillary tangles. Confocal microscopy confirmed co-localization of amyloid-β protein and selenoprotein P. These findings suggest an association of selenoprotein P with Alzheimer's pathology. Show more

Keywords: Alzheimer's disease, amyloid-β, antioxidant, human cortex, neurofibrillary tangle, oxidative stress, selenoprotein, selenoprotein P

DOI: 10.3233/JAD-2008-15313

Citation: Journal of Alzheimer's Disease, vol. 15, no. 3, pp. 465-472, 2008

Authors: Kamat, Chandrashekhar D. | Gadal, Sunyana | Mhatre, Molina | Williamson, Kelly S. | Pye, Quentin N. | Hensley, Kenneth

Article Type: Review Article

Abstract: Oxidative damage is strongly implicated in the pathogenesis of neurodegenerative diseases including Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease and stroke (brain ischemia/reperfusion injury). The availability of transgenic and toxin-inducible models of these conditions has facilitated the preclinical evaluation of putative antioxidant agents ranging from prototypic natural antioxidants such as vitamin E (α-tocopherol) to sophisticated synthetic free radical traps and catalytic oxidants. Literature review shows that antioxidant therapies have enjoyed general success in preclinical studies across disparate animal models, but little benefit in human intervention studies or clinical trials. Recent high-profile failures of vitamin E trials in Parkinson's …disease, and nitrone therapies in stroke, have diminished enthusiasm to pursue antioxidant neuroprotectants in the clinic. The translational disappointment of antioxidants likely arises from a combination of factors including failure to understand the drug candidate's mechanism of action in relationship to human disease, and failure to conduct preclinical studies using concentration and time parameters relevant to the clinical setting. This review discusses the rationale for using antioxidants in the prophylaxis or mitigation of human neurodiseases, with a critical discussion regarding ways in which future preclinical studies may be adjusted to offer more predictive value in selecting agents for translation into human trials. Show more

Keywords: Alzheimer's disease, amyotrophic lateral sclerosis, antioxidants, Huntington's disease, neurodegeneration, neuroinflammation, Parkinson's disease, tocopherols

DOI: 10.3233/JAD-2008-15314

Citation: Journal of Alzheimer's Disease, vol. 15, no. 3, pp. 473-493, 2008

Authors: Koppel, Jeremy | Davies, Peter

Article Type: Review Article

Abstract: The endocannabinoid system is rapidly emerging as a potential drug target for a variety of immune-mediated central nervous system diseases. There is a growing body of evidence suggesting that endocannabinoid interventions may have particular relevance to Alzheimer's disease. Here we present a review of endocannabinoid physiology, the evidence that underscores its utility as a potential target for intervention in Alzheimer's disease, and suggest future pathways of research.

Keywords: Alzheimer's disease, CB1, CB2, dementia, endocannabinoids

DOI: 10.3233/JAD-2008-15315

Citation: Journal of Alzheimer's Disease, vol. 15, no. 3, pp. 495-504, 2008

Article Type: Announcement

DOI: 10.3233/JAD-2008-15316

Citation: Journal of Alzheimer's Disease, vol. 15, no. 3, pp. 505-506, 2008