Volume 1, Number 1, March 1998

Pages 1-34
Paul Averback, David Morse, Hossein Ghanbari
Bursting Dense Microspheres (Spherons) in Alzheimer's Disease: A Review of Studies (1980-1997) on Spherons and the Pathogenesis of
Alzheimer's Disease
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 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.

Pages 35-44
Xue-Qing Chen, John R. Fawcett, Yueh-Erh Rahman, Thomas A. Ala and William H. Frey II
Delivery of Nerve Growth Factor to the Brain via the Olfactory Pathway
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 adjacent 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.

Pages 45-55
George Perry, Rudy J. Castellani, Keisuke Hirai and Mark A. Smith
Reactive Oxygen Species Mediate Cellular Damage in Alzheimer Disease
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 dames lipids, proteins and nucleic acids and results in redox-active metal accumulations, mitochondrial damage and formations of advanced glycation endproducts.  Interesting, ß-protein precursor, amyloid-ß, 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.

Pages 57-59
William K. Summers
Bismuth Toxicity Masquerading Alzheimer's Dementia
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 mg/L (normal is 65 mg/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.

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