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

Authors: Averback, Paul | Morse, David | Ghanbari, Hossein

Article Type: Research Article

Abstract: This paper reviews our research studies during the past 17 years on the relationship of cerebral protein dense microspheres (DMS), termed spherons, and senile plaques (SP) in the aged human brain and in AD. Initially, correlative anatomical and pathological data suggested that spherons may evolve into SP. This led to morphometric studies which strongly supported the theory. Biochemical studies were undertaken which showed that spherons could be isolated to homogeneity from brain tissue and contained the markers associated with SP. Experiments in vitro with spherons, and with inoculation of spherons into animals, reproduced SP lesion characteristics. To test the validity …of using spherons for drug screening, experimental drugs were tested, a few of which are capable of blocking the formation of spheron-induced experimental SP. Show more

DOI: 10.3233/JAD-1998-1101

Citation: Journal of Alzheimer's Disease, vol. 1, no. 1, pp. 1-34, 1998

Authors: Chen, Xue-Qing | Fawcett, John R. | Rahman, Yueh-Erh | Ala, Thomas A. | Frey II, William H.

Article Type: Research Article

Abstract: Purpose: To assess the potential of delivering nerve growth factor (NGF) to the brain along the olfactory neural pathway for the treatment of Alzheimer’s disease. Methods: Recombinant human NGF (rhNGF) was given as nose drops to anesthetized rats. The rhNGF concentrations in the brain were determined by enzyme-linked immunosorbent assay (ELISA). Results: Following olfactory administration, rhNGF reached the brain within an hour, achieving a concentration of 3400 pM in the olfactory bulb, 660–2200 pM in other brain regions and, 240 pM and 180 pM in the hippocampus and the amygdala, respectively. In contrast, little or no …rhNGF was found in the brain following intravenous administration. Conclusions: A significant amount of rhNGF can be delivered to the brain via the olfactory pathway. The detection of rhNGF by ELISA indicates that rhNGF is delivered to the brain relatively intact. The rapid appearance of rhNGF in the brain suggests that it may be transported by an extraneuronal route into the brain via intercellular clefts in the olfactory epithelium. Further work to clarify the transport mechanism is underway. The olfactory pathway is a promising, non-invasive route for drug delivery to the brain, which has potential for the treatment of neurodegenerative diseases including Alzheimer’s disease. Show more

Keywords: nerve growth factor , olfactory, drug delivery, brain, Alzheimer's disease

DOI: 10.3233/JAD-1998-1102

Citation: Journal of Alzheimer's Disease, vol. 1, no. 1, pp. 35-44, 1998

Authors: Perry, George | Castellani, Rudy J. | Hirai, Keisuke | Smith, Mark A.

Article Type: Research Article

Abstract: The two most striking features of Alzheimer disease are (i) the multitude of abnormalities affecting essentially every system and (ii) the strict age dependence. Recent work suggests that both features are linked to increased oxidative stress that damages lipids, proteins and nucleic acids and results in redox-active metal accumulations, mitochondrial damage and formation of advanced glycation endproducts. Interestingly, β-protein precursor, amyloid-β, presenilins, and apolipoprotein E have all been linked to reactive oxygen species production or apoptosis, a process intimately associated with oxidative stress. In therapeutics, the commonality between a number of efficacious agents appears to be oxidative stress reduction. Therefore, …we contend that oxidative stress is the element that links the multitude of changes in Alzheimer disease and that a reduction of oxidative stress will have a dramatic effect on reducing the incidence or progression of Alzheimer disease. Show more

DOI: 10.3233/JAD-1998-1103

Citation: Journal of Alzheimer's Disease, vol. 1, no. 1, pp. 45-55, 1998

Authors: Summers, William K.

Article Type: Case Report

Abstract: A 76-year old white married female had rapid onset dementia with myoclonus and was admitted to an HMO hospital where she was initially diagnosed as Alzheimer's disease. The physician-husband suggested that the condition might be due to the Pepto-Bismol which she had taken chronically to control her irritable bowel syndrome. An elevated serum bismuth level of 242 μg/L (normal is 5 μg/L) established bismuth toxicity as the cause of the dementia. With treatment the patient returned to a normal mental state. The possibility of bismuth encephalopathy needs to be considered in the differential diagnosis of possible Alzheimer's dementia.

DOI: 10.3233/JAD-1998-1104

Citation: Journal of Alzheimer's Disease, vol. 1, no. 1, pp. 57-59, 1998