Faculty Bibliography

Cerebrospinal fluid (CSF) from patients with Alzheimer's disease (AD) and controls was analyzed by one- and two-dimensional gel electrophoresis, electron microscopy, and fluorescence microscopy with thioflavin S staining. In CSF from patients with AD, abnormal proteins were found following two-dimensional gel electrophoresis and silver staining. In CSF samples from most of the AD patients studied, a highly argentophilic material was detected upon silver staining the stacking gel of the one-dimensional gels. Electron microscopy of material eluted from the stacking gel showed fibers of approximately 7-10 nm diameter, with some twisting; properties consistent with paired helical filaments or amyloid. Furthermore, material with the characteristics of amyloid (fiber diameter ranging from 4-10 nm) was found in the CSF sediment. The CSF from AD patients had significantly elevated numbers of yellow fluorescent particles following thioflavin S staining when compared with age-matched, other neurological disease controls. We did not see an increase in autofluorescence, indicating that thioflavin S staining is specific. Our data suggest that AD CSF contains plaque amyloid and possibly proteins from neurofibrillary tangles. The thioflavin S staining method appears to have potential for development as a diagnostic tool

The cholinergic hypothesis of memory dysfunction has guided most of the recent proposals for treating the primary symptoms of AD. The efficacy of these treatments has been severely limited. This review examines two major lines of evidence which suggest that the cholinergic hypothesis may have to be expanded and revised. The cholinergic hypothesis focuses on pre-synaptic defects. It assumes cholinoceptive neurons would function normally with adequate stimulation. Evidence is not sufficient to support this assumption. In addition, dissociations have been demonstrated between muscarinic receptor number and functional response of cholinoceptive neurons. Various measures are proposed to investigate the functional integrity of muscarinic receptors in AD patients. AD often has been characterized as a disorder produced by generalized cholinergic hypoactivity. Evidence for cortisol hypersecretion, abnormal dexamethasone suppression, and the occurrence of depressive symptoms, motoric dysfunction and sleep abnormalities in AD patients is more consistent with regional cholinergic hyperactivity than generalized hypoactivity. Resolution of these discrepancies could shed new light on the pathophysiology and treatment strategies for AD. Cholinoceptive neurons could be hypersensitive, subsensitive or have unaltered responsivity. These options would have very different treatment implications. New developments in outcome assessment which are capable of discriminating varieties of differential response to treatment can spur treatment development and improve quality of care for patients with complex disorders such as AD

Protein patterns of cerebrospinal fluid (CSF) from patients with spasmodic torticollis (ST) were investigated to determine whether abnormalities previously reported could be detected and further identified. CSF was collected from 12 patients with ST and 6 normal controls. The CSF proteins were analyzed using sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis and silver staining. In 11 of the 12 patients with ST, a CSF protein pattern was observed which differed from that in the controls. The identity of the abnormal proteins was ascertained by blotting and immunostaining with specific antisera to IgG and ceruloplasmin (Cp). CSF from 2 of 12 patients had distinct bands staining for IgG and 7 had abnormal immunostaining for Cp

Despite a dramatic increase in the understanding of the neuropathologic and neurochemical alterations accompanying Alzheimer's disease, by far the largest cause of progressive and incapacitating cognitive dysfunction in the elderly, physicians have as yet no pharmacologic agent that can be prescribed safely either to arrest or reverse this decline. This lack of effective therapeutic agents is contributing to the use by an increasing number of health professionals, including physicians and concerned families, of unproved, costly, and potentially dangerous modalities, such as chelation therapy. The purpose of this paper is to describe some individuals with Alzheimer-type dementia who have undergone chelation therapy

The effects of diazepam on memory and psychomotor performance in healthy elderly (N = 12) and young (N = 12) individuals were examined. Diazepam was administered acutely in a single, oral 2.5 mg dose. Diazepam impaired memory, both immediate and delayed recall, and psychomotor performance in the elderly subjects. In addition, the drug caused an increase in self-reported sedation in elderly subjects but not in young subjects. These findings suggest an age-related increase in the sensitivity of elderly individuals to the central depressant effects of diazepam