Analyzing Gene Expression from Whole Tissue vs. Different Cell Types Reveals the Central Role of Neurons in Predicting Severity of Alzheimer’s Disease

Alterations in gene expression resulting from Alzheimer’s disease have received considerable attention in recent years. Although expression has been investigated separately in whole brain tissue, in astrocytes and in neurons, a rigorous comparative study quantifying the relative utility of these sources in predicting the progression of Alzheimer’s disease has been lacking. Here we analyze gene expression from neurons, astrocytes and whole tissues across different brain regions, and compare their ability to predict Alzheimer’s disease progression by building pertaining classification models based on gene expression sets annotated to different biological processes. Remarkably, we find that predictions based on neuronal gene expression are significantly more accurate than those based on astrocyte or whole tissue expression. The findings explicate the central role of neurons, particularly as compared to glial cells, in the pathogenesis of Alzheimer’s disease, and emphasize the importance of measuring gene expression in the most relevant (pathogenically ‘proximal’) single cell types.     

Incorporation of mitochondrial membrane proteins into liposomes containing acidic phospholipids.

Cytochrome oxidase, QH2-cytochrome c reductase, and the oligomycin-sensitive adenosine triphosphatase were incorporated into liposomes by a new procedure which yielded unidirectional orientation of the proteins. Cytochrome oxidase was reconstituted in the mitochrondrial orientation and the adenosine triphosphatase in the submitochondrial orientation. Reconstitutions were achieved by incubating the proteins at room temperature with liposomes which contained phosphatidylcholine, phosphatidylethanolamine, and an acidic phospholipid (cardiolipin, phosphatidylinositol, or phosphatidylserine). The incorporation occurred without added detergent or sonication. This incorporation procedure may serve as a model for the insertion of proteins in vivo.     

Septal and Hippocampal Glutamate Receptors Modulate the Output of Acetylcholine in Hippocampus: A Microdialysis Study

Abstract: In the present study, glutamate receptor agonists and antagonists were administered by retrograde microdialysis into either the medial septum/vertical limb of the diagonal band (MS/vDB), or hippocampus, and the output of acetylcholine (ACh) was measured in the hippocampus by using intracerebral microdialysis. Perfusion with N -methyl- d -aspartate (NMDA) and ( S )-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) in the MS/vDB caused an increase in ACh output in the hippocampus. This increase was completely blocked by coadministration of their respective antagonists d (−)-2-amino-5-phosphonopentanoic acid ( d -AP5) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Perfusion in the MS/vDB with kainic acid also caused an increase in ACh output, but coadministration of CNQX attenuated the increase only partially. Perfusion with d -AP5 or CNQX alone in the septal probe did not affect ACh output from the hippocampus. In contrast to the results of septal administration of NMDA and AMPA, local perfusion with the same drugs in the hippocampus caused a decrease in ACh output. Whereas the results of septal administration of drugs indicate that septal cholinergic neurons probably receive excitatory glutamatergic innervation, the decrease in ACh output caused by administration of NMDA and AMPA in the hippocampus is poorly understood.     

Reconsidering the relation between serum homocysteine and red blood cell distribution width: a cross-sectional study of a large cohort

Purpose: In a recent small sample study, red blood cell distribution width (RDW) was suggested as a predictor of homocysteine levels. The current study was aimed to reexamine this association in a large scale sample.

Methods: A retrospective cross-sectional study of healthy adults, conducted at Rabin Medical Center, during 2000–2014. Data were retrieved from the medical charts and a logistic regression controlling for interfering factors was carried out. Sensitivity analysis was implemented by exclusion of individuals with anaemia.

Results: Five thousand, five hundred fifty-four healthy individuals were included. Mean serum homocysteine level was 10.10 (SD 2.72) μmol/L. 34.4% of the study population had a homocysteine level higher than the upper limit of normal (10.8?μmol/L). Homocysteine showed no association with RDW (OR 1.00; 95% CI 0.97–1.03), but increased with age (OR 1.05; 95% CI 1.04–1.06) and decreased with a rise in haemoglobin (OR 0.77; 95% CI 0.71–0.83), and in the mean corpuscular volume (OR 0.86; 95% CI 0.85–0.88). Exclusion of individuals with anaemia did not reveal an association between homocysteine and RDW but found a somewhat smaller association between haemoglobin and RDW [OR 0.82; 95% CI 0.73–0.91].

Conclusions: In our large scale sample we did not find an association between RDW and serum homocysteine.     

Biogenesis of chloroplast membranes: XIV. Inhomogeneity of membrane protein distribution in photosystem particles obtained from Chlamydomonas reinhardi. Y-l

Treatment of chloroplast membranes of Chlamydomonas reinhardi with Triton-× 100 yielded membrane particles which were resolved into three bands on discontinuous sucrose gradients. One of these was enriched in the chlorophyll absorption and fluorescence properties and photosynthetic activities consistent with photosystem I enrichment, while another had the chlorophyll absorption and fluorescence properties expected to photosystem II enriched particles. The third type of particle was enriched in chlorophyll species which are probably the bulk chlorophylls of photosystem I. Analysis of the proteins of these fractions by polyacrylamide electrophoresis indicated substantial differences, the most striking being that the photosystem II particle type was greatly enriched in the major species of chloroplast membrane protein. Previous work has shown this to be an important protein controlling membrane assembly. This protein was depleted in the photosystem I particle type. We interpret this data to indicate a lack of homogeneity in the distribution of membrane proteins in the chloroplast membranes of Chlamydomonas, at the level of the two photosystems.