Smoking affects the phenotype of Alzheimer disease.

Because epidemiologic and in vitro evidence conflict, the authors studied the association between smoking and Alzheimer disease (AD) in 46 never, 47 former, and 15 active smokers with AD followed to autopsy. Disease parameters were examined by smoking status and amount smoked in bivariate tests and in multivariate models controlling for age, sex, education, and APOE status. Smoking status was not associated with cognitive or neuropathologic measures. However, active smokers were significantly younger at death and higher levels of smoking were associated with shorter disease duration.

Hippocampal sclerosis contributes to dementia in the elderly.

OBJECTIVE: To assess the relevance of hippocampal sclerosis (HS) to dementia in the elderly. BACKGROUND: HS is a prominent pathologic finding in some demented elderly, but the anatomic substrate and cognitive profiles of this dementia have not been well established. DESIGN/METHODS: An autopsy series, including dot-immunobinding assay to estimate neocortical synaptic density, of eight patients (three men, five women) with HS on whom extensive antemortem neuropsychological testing was available. RESULTS: Mean age at onset was 72.0 (+/-9.8) (range, 59 to 89) with a mean duration of symptoms of 6.5 (+/-2.9) years. Patients were only mildly impaired with a mean MMSE of 20.9 (+/-4.9) and a mean DRS of 103.1 (+/-12.5) at presentation. Cardiovascular disease was present in 88%, with a mean Hachinski score of 3.4 (+/-2.2). No patient had a history of seizures. Sixty-three percent had depression or depressive symptoms. Neuropsychologically, most patients presented with prominent memory and language deficits and became progressively demented. Neuropathologically, isolated HS was a rare finding; many patients had either very mild or neocortical "plaque only or plaque predominant" Alzheimer's disease (AD) in addition to HS changes. Midfrontal neocortical synaptophysin counts were significantly reduced in all HS patients compared with controls (p = 0.0006). CONCLUSIONS: In the elderly, HS can be a neuropathologic substrate of dementia. Clinically, it can be associated with a course that is difficult to distinguish from AD although cardiac disease and depression are frequent concomitants. Deterioration of cognitive function in these subjects may relate to other pathologic features such as neocortical synapse loss.

A simple dot-immunobinding assay for quantification of synaptophysin-like immunoreactivity in human brain.

Neocortical decreases in synaptic density correlate significantly with the cognitive impairment seen in Alzheimer disease. Recently available monoclonal antibodies (MAb) have made possible the highly specific and sensitive detection of synapse-associated proteins in immunocytochemical and immunochemical techniques. We describe a simple yet highly sensitive dot-immunobinding assay for relative quantification of the synapse marker protein synaptophysin in human brain homogenate fractions with the mouse MAb SY38. Fractions prepared from control and Alzheimer specimens were blotted to nitrocellulose membranes and reacted with SY38, rabbit secondary antibody, and iodinated protein A. A relative standard curve was constructed to normalize results from multiple assay runs. We correlated the results with the more complex immunocytochemical synaptic density measurement technique of immunolabeling coupled with laser confocal imaging, showing good correlation at r = 0.821. Results from Alzheimer cases showed a 40% decrease in synaptophysin immunoreactivity in midfrontal cortex compared with normal controls.

Urea movement across erythrocyte membrane during artificial kidney treatment.

Previous work by other investigators indicates that erythrocyte urea and creatinine in uremic whole blood leaving the hemodialyzer do not move down the concentration gradients established by loss of these solutes across the dialyzer membrane. This puzzling disequilibrium is at odds with work indicating ready movement of both solutes across the erythrocyte membrane of nonuremic erythrocytes studied in vitro. The present study shows that contact with the dialyzer does not noticeably alter the erythrocyte membrane of the uremic patient, so that urea distribution between plasma and erythrocyte water is the same as that in the blood of normal control subjects. Furthermore, urea does not show a disequilibrium in concentration across the erythrocyte membrane in response to 50% dilution with a modified Ringer's solution but rather equilibrates swiftly and completely.