Neural membrane phospholipids in Alzheimer disease.

Phospholipids form the backbone of neural membranes, providing fluidity and permeability. Two plasma membrane fractions, one from synaptosomes (SPM), the other from glial and neuronal cell bodies (PM), were prepared from different regions of autopsied Alzheimer disease (AD) brains. Corresponding fractions were prepared from age-matched control brains. All fractions from AD brains showed significantly lower levels of ethanolamine glycerophospholipids and significantly higher levels of serine glycerophospholipids than the control brain. No differences were observed in phosphatidylcholine levels among these membranes. These results suggest that altered phospholipid composition of plasma membranes may be involved in the abnormal signal transduction and neurodegeneration in AD.

The GenePrint Light method for Southern transfer and chemiluminescent detection of human genomic DNA.

A simple, fast and sensitive method to perform Southern transfer and hybridization with nonradioactive detection of genetic loci is described. With a 10-ng sample of human genomic DNA, alleles of the D2S44 locus can be detected within 7 h of completing gel electrophoresis.

Quantitation of photic driving in dementia with normal EEG.

The EEG is frequently normal when early dementia is clinically suspected. The presence or absence of occipital driving with intermittent photic stimulation is not helpful in detecting cerebral pathology, but quantitation of photic driving was shown to distinguish between dementia and depression in geriatric patients. We quantified photic driving in twenty clinically demented patients without diffuse or focal EEG abnormality, and compared this in 20 age-matched normal controls. Intermittent stimulation at odd-numbered frequencies between 1 and 31 Hz was carried out. The product of frequency of stimulation and duration of driving response was determined, and the incidence of absent, subharmonic and supraharmonic photic driving was determined. The quantitative measure of frequency times following duration was significantly greater in the nondemented individuals than in demented patients with normal EEGs. More nondemented individuals demonstrated supraharmonic and subharmonic responses than did demented patients. The range of normal variability in persistence, duration, and symmetry of photic driving is great, and caution in determining abnormality on this basis is appropriate. Subtle but measurable changes in photic driving may occur early in dementing illnesses, however.

Stimulation of lipolytic enzymes in Alzheimer's disease.

The activities of monoacylglycerol and diacylglycerol lipases were 6 to 8 times higher in plasma membrane and synaptosomal plasma membrane fractions of nucleus basalis from patients with Alzheimer's disease than in those membranes from normal human brains. Membranes from the hippocampus region of Alzheimer-affected brains also showed consistently higher activities of monoacylglycerol and diacylglycerol lipases than those from control brains. These results indicate a stimulation of lipolytic enzymes in nucleus basalis and hippocampus regions in patients with Alzheimer's disease.

Effects of secA mutations on the synthesis and secretion of proteins in Escherichia coli. Evidence for a major export system for cell envelope proteins.

We have followed the synthesis and secretion of a number of periplasmic and outer membrane proteins in three strains of Escherichia coli, a secA amber mutant, a secA temperature-sensitive mutant, and a strain that blocks protein secretion due to a high level of expression of an export-defective hybrid protein between maltose-binding protein and beta-galactosidase (MalE-LacZ). Our results show that after several hours under nonpermissive conditions the specificity and extent of the export blocks in the secA temperature-sensitive mutant and the strain producing the MalE-LacZ hybrid protein are identical, affecting at least four major outer membrane proteins and most but not all periplasmic proteins. The secA gene product, therefore, appears to be an essential component of the major export pathway in E. coli which is used by many envelope proteins independent of whether they are cotranslationally or post-translationally secreted. In contrast, the synthesis of only a subset of these envelope proteins is reduced in the secA amber mutant after shift to the nonpermissive condition. These results indicate that the SecA protein serves roles both in the synthesis and the secretion of certain cell envelope proteins.

Export defect adjacent to the processing site of staphylococcal nuclease is suppressed by a prlA mutation.

Plasmids have been constructed in which the Escherichia coli alkaline phosphatase promoter and signal sequence have been fused to the staphylococcal nuclease gene to promote the high-level expression and secretion of this gene product in E. coli. We determined that the first amino acid residue after the signal sequence can determine whether this protein was processed and exported to the periplasmic space. Fractionation and protease accessibility studies were used to show that the export-defective, nuclease precursor is internal to the cytoplasmic membrane barrier of the cell. Furthermore, this export defect was suppressed in a strain containing a prlA mutation. These findings are novel in that this region of the polypeptide chain has been implicated in processing but not export and that prlA mutations have not been previously known to suppress such defects.

[Relative spacing of the microtubules and intermediate filaments during fibroblast spreading in culture]. / Vzaimnoe raspolozhenie mikrotrubochek i promexhutochnykh filamentov pri rasplastyvanii fibroblastov v kul'ture.

Using double immunofluorescence staining, microtubules and intermediate filaments were shown to have similar distribution in the substrate-spread mouse embryo fibroblasts. However, in cells spreading on the substrate, microtubules grow from the centre to the periphery regions quicker than intermediate filaments. We suppose that microtubules may guide the spreading of intermediate filaments from the perinuclear regions to the periphery of the cell during its spreading.

prlA-mediated suppression of signal sequence mutations is modulated by the secA gene product of Escherichia coli K-12.

We studied the dependence of prlA-mediated suppression of signal sequence mutations in maltose-binding protein on cellular SecA levels in Escherichia coli. Reduction of SecA levels within the cell had strong positive and negative effects on prlA-mediated suppression, depending on the particular signal sequence mutations involved. This finding suggests that prlA and secA gene products are both components of a common export system.

The relationship between cognitive status and visual information processing.

The present investigation involved an examination of susceptibility to visual masking of older adults displaying evidence of Alzheimer's disease and healthy, cognitively intact older adults. Results indicated that the cognitively impaired group was more susceptible to the perceptual interference of a visual mask than was the cognitively intact group. In addition, the impaired group was found to be particularly susceptible to masking by a visual pattern (which had similar figural characteristics to target stimuli) as compared to masking by random noise (which had figural characteristics unrelated to the target). Finally, susceptibility to masking was found to be negatively correlated with performance on the Information subtest of the Wechsler Adult Intelligence Scale-Revised and with rated level of cognitive functioning. It was concluded that this pattern of results represents an acceleration of changes in perceptual processing typically associated with normal human aging.

Age-related neuropsychological deficits in Down's syndrome.

Down's syndrome (DS) has been suggested as a high-risk condition for Dementia Alzheimer's type (DAT). In the present study, neuropsychological variables were assessed in 165 DS subjects and 163 matched mentally retarded controls. Overall, DS subjects had lower scores for orientation, digit span, visual memory, object-naming, and general knowledge, as well as more "released" reflexes. Impairments were most evident in DS subjects greater than 50 years old. These findings provide further support for an association between aging and DAT in Down's syndrome. Methodological issues and areas for future research are discussed.

Clinical evaluation of dementia in Down's syndrome: a preliminary report.

Down's syndrome residents were found to have significantly greater impairment on measures of orientation, attention span, digit span recall, visual memory, object identification and praxis, and were more likely to have pathological released reflexes than age and IQ matched controls. Neuropsychiatric status tended to worsen with advancing age in Down's syndrome, but not in controls. Forty-five percent of DS individuals age 45 or older had a full syndrome of dementia, compared to only 5% of controls. Although further research is necessary, particularly employing larger samples and more detailed medical screening, these results support the association of dementia Alzheimer type with Down's syndrome.

Late onset spinal muscle atrophy--a sex linked variant of Kugelberg-Welander.

A syndrome of progressive muscular atrophy in reported in male members of a Caucasian family. Two affected members were examined in detail, one with post mortem. Fasciculations and atrophy of tongue as well as of the proximal limb muscles were observed, and there was profound weakness of the proximal muscles. The EMG and muscle biopsy were consistent with a neurogenic disease. The most pronounced lesion was in the lateral part of the anterior horn, with minimal involvement of the ventral portion of the anterior horns and sparing of the neurons of Clarke's column. Two earlier families with possible Kugelberg-Welander syndrome have been reported in which a sex-linked form also seems probable, and the varied inheritance pattern and uncertain pathological correlations suggest that the Kugelberg-Welander and familial amyotrophic lateral sclerosis both represent heterogenous neurological disorders.