Journal of Alzheimer's Disease - Volume 10, issue 1

Authors: Larner, A.J. | Keynes, R.J.

Article Type: Research Article

Abstract: Aberrant neurite growth is one of the neuropathological signatures of the Alzheimer's disease brain, both around amyloid plaques and in the cortical neuropil. Disruption of neuroinhibitory or repulsive growth and guidance signals, as well as of neurotrophic or permissive signals, may contribute to this dystrophic growth. Hence, therapeutic efforts directed exclusively at restoring neurotrophic activity are unlikely to meet with success. The molecular species responsible for neuroinhibitory effects in the Alzheimer's disease brain are beginning to be elucidated.

Keywords: Alzheimer disease, growth factors, neuroinhibitors

DOI: 10.3233/JAD-2006-10111

Citation: Journal of Alzheimer's Disease, vol. 10, no. 1, pp. 75-80, 2006

Authors: Chohan, Muhammad Omar | Iqbal, Khalid

Article Type: Research Article

Abstract: Glutamate toxicity through NMDA receptor channels has long been central to the understanding of acute neuronal injury. Recent studies implicate similar events in chronic neurodegenerative diseases. Here, we analyze some of the most intriguing evidence for NMDA receptor-mediated cellular dysfunction and propose a mechanism by which hyperactive NMDA receptors might lead to neurofibrillary degeneration in Alzheimer's disease.

Keywords: Alzheimer's disease, tau, hyperphosphorylation, glutamate toxicity, NMDA receptors, memantine

DOI: 10.3233/JAD-2006-10112

Citation: Journal of Alzheimer's Disease, vol. 10, no. 1, pp. 81-87, 2006

Authors: de la Monte, Suzanne M. | Tong, Ming | Lester-Coll, Nataniel | Plater, Jr., Michael | Wands, Jack R.

Article Type: Research Article

Abstract: Alzheimer's disease (AD) is associated with major impairments in insulin and insulin-like growth factor (IGF) gene expression and signaling in the brain. These abnormalities increase with severity of dementia, and are associated with deficiencies in energy metabolism and acetylcholine homeostasis. The co-existence of brain insulin/IGF deficiency and resistance suggests that AD may represent a brain-specific form of diabetes, i.e. Type 3 diabetes. This hypothesis is supported by the findings in an experimental animal model in which intracerebral (ic) Streptozotocin (STZ) was used to deplete brain and not pancreatic insulin. The ic-STZ treatment produced brain-specific insulin depletion and insulin resistance are …associated with progressive neurodegeneration that shares many features in common with AD. We now demonstrate that early treatment with peroxisome-proliferator activated receptor agonists can effectively prevent ic-STZ-induced neurodegeneration and its associated deficits in learning and memory. These effects were mediated by increased binding to insulin receptors, reduced levels of oxidative stress and tau phosphorylation, and increased choline acetyltransferase expression in the brain, suggesting that insulin sensitizer agents may have therapeutic efficacy in early AD. Show more

Keywords: Type 3 diabetes, insulin, Alzheimer's disease, growth factor receptors, RT-PCR, Streptozotocin, peroxisome-proliferator activated receptor, insulin sensitizers, therapy

DOI: 10.3233/JAD-2006-10113

Citation: Journal of Alzheimer's Disease, vol. 10, no. 1, pp. 89-109, 2006

Authors: Thirumangalakudi, Lakshmi | Samany, Pezhman Ghatreh | Owoso, Akinkunle | Wiskar, Brandt | Grammas, Paula

Article Type: Research Article

Abstract: Data are emerging to support the idea that mediators of angiogenesis are found in the Alzheimer's disease (AD) brain. The objective of this study is to compare the expression of the angiogenic mediators vascular endothelial growth factor (VEGF), angiopoietin, and matrix metalloproteinases (MMPs) in the microcirculation of AD patients and age-matched controls. Our results indicate that angiopoietin-2 and VEGF are expressed by AD- but not control-derived microvessels. AD-derived microvessels also release higher levels of MMP-2 and MMP-9 compared to controls. The data show that despite high levels of MMP-9, assessed by western blot, MMP-9 activity is not detectable in AD …microvessels. In this regard we find high levels of the tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) in AD, but not control vessels. Furthermore, we explore the ability of thrombin, previously shown to be present in AD microvessels, to affect TIMP expression in cultured brain endothelial cells and find that thrombin causes up regulation of TIMP-1. These data show that angiogenic changes occur in the microcirculation of the AD brain and suggest that if these changes are contributory to disease pathogenesis, targeting the abnormal brain endothelial cell would provide a novel therapeutic approach for the treatment of this disease. Show more

Keywords: Alzheimer's disease, angiogenic proteins, microvessels, inflammation, thrombin

DOI: 10.3233/JAD-2006-10114

Citation: Journal of Alzheimer's Disease, vol. 10, no. 1, pp. 111-118, 2006

Article Type: Book Review

DOI: 10.3233/JAD-2006-10115

Citation: Journal of Alzheimer's Disease, vol. 10, no. 1, pp. 119-120, 2006

Article Type: Discussion

DOI: 10.3233/JAD-2006-10116

Citation: Journal of Alzheimer's Disease, vol. 10, no. 1, pp. 121-130, 2006

Article Type: Announcement

DOI: 10.3233/JAD-2006-10117

Citation: Journal of Alzheimer's Disease, vol. 10, no. 1, pp. 131-132, 2006