Platelet membrane abnormality in Alzheimer's disease.

Fluorescence studies of membrane fluidity were conducted double-blind using platelet and red cell membranes prepared from 24 demented patients with probable Alzheimer's disease and 36 neurologically healthy subjects. The fluidity of the hydrocarbon and lipid-aqueous interface regions of cell membranes was determined at 37 degrees C by fluorescence spectroscopy using the lipid probes 1,6-diphenyl-1,3,5-hexatriene (DPH) and 1-[4-(trimethylamino)phenyl]-6-phenyl-1,3,5-hexatriene (TMA-DPH), respectively. The rotation rate of TMA-DPH in labeled platelet membranes did not differ between the groups. In contrast, the rotation rate of DPH in labeled platelet membranes from the demented patients (2.15 +/- 0.24 X 10(8)/sec, SD) was greater than that for the normal controls (1.93 +/- 0.13 X 10(8)/sec, SD, p = 3.8 X 10(-5)). This difference was reflected by a reduction in the steady-state anisotropy of DPH in labeled platelets from the demented group (0.1887 +/- 0.0085, SD) when compared to the respective mean for the controls (0.2000 +/- 0.0060, SD; p = 1.3 X 10(-7)). Abnormal membrane fluidity was significantly correlated with severity of dementia, but not with duration of illness or apparent age of onset. The findings do not support the hypothesis that Alzheimer's disease results from a pathological acceleration of the normal aging process, since normal aging is associated with decreased fluidity of cell membranes from platelets, as well as from lymphocytes, hepatocytes, and neurons.

Proliferation of internal membranes in platelets from patients with Alzheimer's disease.

Platelets from six moderately demented patients with probable Alzheimer's disease (NINCDS-ADRDA criteria) and six neurologically healthy controls were examined by electron microscopy. While platelet preparations from the control group contained infrequent examples (4.6%) of platelets with an unusually abundant internal system of smooth membranes, the frequency of these atypical cells (15.5%) was over three times higher in the samples prepared from the demented patients (p = 2.2 X 10(-2)). Consistent with our previous reports, platelet membranes from the Alzheimer's disease group exhibited a significant increase in membrane fluidity, as reflected by the rotation rate and fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene (DPH) at 37 degrees C. Moreover, membrane fluidity was correlated with the frequency of atypical platelets visualized by electron microscopy. Since internal platelet membranes have been reported to be more fluid than external platelet membranes, these and other results presented suggest that the increase in platelet membrane fluidity associated with Alzheimer's disease may be the result of a dysregulation of platelet membrane biosynthesis.

Platelet membrane fluidity identifies a clinical subtype of Alzheimer's disease.

1. The fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene (DPH) in labeled platelet membranes, an index of membrane fluidity, identifies a prominent subgroup (approx. 50%) of patients with Alzheimer's disease who manifest distinct clinical features. 2. We review an integrated series of studies that explore both the clinical significance of this finding and the biological basis for the platelet membrane alteration.

Flagellar morphology in stumpy-flagella mutants of Chlamydomonas reinhardtii.

Sixteen new mutants of the biflagellate green alga Chlamydomonas reinhardtii with either stumpy-flagella or no flagella at all were examined by electron microscopy. Four of the mutants were found to carry short bulbous flagella containing amorphous electron-dense material which may represent unassembled flagellar protein. Basal bodies of normal ultrastructure were present in all mutants. Dikaryon dominance tests indicated that the stumpy mutations were recessive to wild-type in all cases tested. Stumpy mutations also conferred a measure of detergent resistance to Chlamydomonas, apparently by affecting the detergent-solubility of the flagellar membrane.

Abnormal basal-body number, location, and orientation in a striated fiber-defective mutant of Chlamydomonas reinhardtii.

We describe a mutant of Chlamydomonas reinhardtii in which basal body associated striated fibers are absent or incomplete. Basal body spacing, angle, and relative rotational orientation are abnormal and extremely variable. Abnormal partitioning of cellular contents at cytokinesis is also evident. Mating, maintenance of flagellar length equality, and backward swimming response are normal. Genetic analysis indicates mutation of a new Mendelian gene--vfl-3--linked to the centromere of Chromosome VI.

Ultrastructure of microfilament bundles in baby hamster kidney (BHK-21) cells. The use of tannic acid.

After standard glutaraldehyde-osmium tetroxide fixation procedures, the majority of microfilament bundles in BHK-21 cells exhibit relatively uniform electron density along their long axes. The inclusion of tannic acid in the glutaraldehyde fixation solution results in obvious electron density shifts along the majority of microfilament bundles. Striated patterens are frequently observed which consist of regularly spaced electron dense (D) and electron lucid (L) bands. A striated pattern is also observed along many BHK-21 stress fibers after processing for indirect immunofluorescence utilizing BHK-21 myosin antiserum. A direct correlation of these periodicities seen by light and electron microscope techniques is impossible at the present time. However, comparative measurements indicate that the overall patterns seen in the immunofluorescence and electron microscope preparations are similar. The ultrastructural results provide an initial clue for the ultimate determination of the supramolecular organization of contracile proteins other than actin within the microfilament bundles of non-muscle cells.

Clustering of the genes for allantoin degradation in Saccharomyces cerevisiae.

We have shown that allantoin degradation in Saccharomyces cerevisiae proceeds exclusively through the intermediate formation of allantoic acid, urea, and allophanic acid. The number of reactions between allantoic acid and urea, however, remains obscure owing to our inability to isolate a mutant defective in ureidoglycolate hydrolase. Structural genes for the enzymes, allantoinase (dal1) and allantoicase (dal2) are located on chromosome IX promixal to the centromere in the order dal1-dal2-lysl.