J. Lipid Res. Neurobiology of Lipids (ISSN1683-5506)
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Journal of Lipid Research, Vol. 42, 1292-1297, August 2001
Copyright © 2001 by Lipid Research, Inc.

Original Article

Amyloid ß-peptide1-40 increases neuronal membrane fluidity: role of cholesterol and brain region

S. V. Chochinaa,b, N. A. Avdulova,b, U. Igbavboaa,b, J. P. Clearya,d, E. O. O'Harea,c, and W. G. Wooda,b
a Geriatric Research, Education and Clinical Center, University of Minnesota, Minneapolis, MN 55417
b VA Medical Center, and Departments of Pharmacology, University of Minnesota, Minneapolis, MN 55417
c Psychiatry, University of Minnesota, Minneapolis, MN 55417
d University of Minnesota School of Medicine, and Department of Psychology, University of Minnesota, Minneapolis, MN 55417

Correspondence to: W. G. Wood, at: VA Medical Center, GRECC, 11G, Minneapolis, MN 55417., Woodx002{at}tc.umn.edu (E-mail)


  ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES

There is increasing evidence of an interaction between cholesterol dynamics and Alzheimer's disease (AD), and amyloid ß-peptide may play an important role in this interaction. Aß destabilizes brain membranes and this action of Aß may be dependent on the amount of membrane cholesterol. We tested this hypothesis by examining effects of Aß1-40 on the annular fluidity (i.e., lipid environment adjacent to proteins) and bulk fluidity of rat synaptic plasma membranes (SPM) of the cerebral cortex, cerebellum, and hippocampus using the fluorescent probe pyrene and energy transfer. Amounts of cholesterol and phospholipid of SPM from each brain region were determined. SPM of the cerebellum were significantly more fluid as compared with SPM of the cerebral cortex and hippocampus. Aß significantly increased (P <= 0.01) annular and bulk fluidity in SPM of cerebral cortex and hippocampus. In contrast, Aß had no effect on annular fluidity and bulk fluidity of SPM of cerebellum. The amounts of cholesterol in SPM of cerebral cortex and hippocampus were significantly higher (P <= 0.05) than amount of cholesterol in SPM of cerebellum. There was significantly less (P <= 0.05) total phospholipid in cerebellar SPM as compared with SPM of cerebral cortex.

Neuronal membranes enriched in cholesterol may promote accumulation of Aß by hydrophobic interaction, and such an interpretation is consistent with recent studies showing that soluble Aß can act as a seed for fibrillogenesis in the presence of cholesterol. — Chochina, S. V., N. A. Avdulov, U. Igbavboa, J. P. Cleary, E. O. O'Hare, and W. G. Wood. Amyloid ß-peptide1-40 increases neuronal membrane fluidity: role of cholesterol and brain region. J. Lipid Res. 2001. 42: 1292;–1297.

Supplementary key words: Alzheimer's disease, lipids, neuron, phospholipid


  INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES

There is increasing evidence of an association between cholesterol and Alzheimer's disease (AD) (1) (2) (3). Recent studies have reported that patients taking 3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitors had a lower prevalence of dementia, including patients diagnosed with AD (4) (5). Apolipoproteins are part of the lipoprotein complex that transports lipids, including cholesterol and apolipoprotein E4,, which has been proposed to be a risk factor for development of AD (6) (7) (8). Abnormal processing of amyloid ß-peptide (Aß), an amphipathic peptide consisting of 39;–42 amino acid residues, is thought to play an important role in the development of AD (9). Aß interacts with cholesterol in two major modes of action: 1) expression of amyloid precursor protein (APP) and Aß are modified by alterations in cholesterol content, and 2) Aß affects cholesterol dynamics such as cellular transport, distribution, and binding [as reviewed in refs. (3), (10)].

Both APP and Aß have been shown to be located in membrane domains enriched in cholesterol (11) (12) (13). The steroid ring of cholesterol resides in the hydrophobic region of membranes and its hydroxyl group is near to the phospholipid ester carbonyl groups (14). There is evidence that soluble Aß prefers the hydrophobic environment of membranes as compared with a hydrophilic environment (15) (16). Aß perturbs biological membranes (16) (17) (18) (19) and this action of Aß may be dependent on membrane cholesterol content. Brain regions differ in lipid composition, including cholesterol content (20) (21), and could be differentially perturbed by Aß. This hypothesis was tested in synaptic plasma membranes (SPM) of cerebral cortex, hippocampus, and cerebellum using energy transfer between tryptophan amino acid residues of SPM proteins and pyrene to determine annular fluidity, or the fluidity of the lipid environment in proximity to proteins. Bulk fluidity was measured in SPM of the three brain regions using the fluorescence intensity of pyrene alone. The sensitivity of these fluorescence techniques has been previously reported using SPM and different treatment conditions (17) (22) (23). Amyloid ß-peptide1-40 was used in the present experiments. We have previously shown that a fragment of Aß1-40, Aß25-35, and Aß1-42 had similar effects on membrane fluidity as Aß1-40 (16) (17). SPM cholesterol content and phospholipid content were also determined in samples of the three brain regions.


  MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES

Chemicals
Aß1-40 (Lot # ZN571) was purchased from Bachem (Torrance, CA). Cholesterol standards and a reagent kit for cholesterol quantification were purchased from Boehringer-Mannheim Diagnostics (Indianapolis, IN). Pyrene and all other chemicals were purchased from Sigma Chemical Company (St. Louis, MO).

SPM preparation
SPM were isolated using discontinuous Ficoll-sucrose gradients and procedures previously reported by our laboratory (17) (24) (25). Three-month-old male Sprague Dawley rats were anesthetized using carbon dioxide and then decapitated. The brain of each rat was removed and the cerebral cortex, hippocampus, and cerebellum were dissected on ice. Tissue was homogenized in a sucrose buffer (0.32 M Sucrose and 5 mM HEPES, pH 7.4) containing 0.5 mM EDTA at 4°C. The homogenate was centrifuged at 578 g for 8 min (SS34 rotor in a Sorvall RC5C centrifuge) and the supernatant removed and centrifuged at 17,300 g for 10 min. The resulting pellet (P2) was suspended in the sucrose buffer and layered over 7.5% and 13% Ficoll solutions (wt/vol: Ficoll/Sucrose buffer) containing 0.5 mM EDTA. The gradients were centrifuged in a SW28 rotor at 80,000 g for 30 min using a Beckman L8-70M ultracentrifuge. The material at the 7.5% and 13% interface was carefully removed, sucrose buffer added, and centrifuged at 17,300 g for 15 min. The pellet enriched in synaptosomes was resuspended in sucrose buffer and centrifuged at 12,000 g for 10 min. SPM were prepared by lysing synaptosomes in 5 mM Tris-HCl (pH 8.5). The synaptosomal suspension was kept on ice (4°C) and vortexed every 20 min for 1 h. The suspension was then centrifuged at 41,000 g for 20 min. The pellet was resuspended in 15 ml cold distilled water and underlayered with 15 ml 0.75 M sucrose buffer containing 1.5 mM Tris, 3 mM HEPES, 0.25mM EDTA (pH 7.4), and centrifuged at 41,000 g for 30 min (SW 28, Beckman L8-70M ultracentrifuge). SPM at the interface were removed and pelleted at 41,000 g for 20 min (SS34 rotor, Sorvall RC5C). The SPM pellet was resuspended in 50 mM Tris, pH 7.4.

Fluorescence spectroscopy
A LS 50-B fluorimeter (Perkin-Elmer, Norwalk, CT) was used to determine fluorescence using procedures previously reported by our laboratory (22) (23) (26). Cuvette temperature was maintained at 36.5°C with a circulating water bath. Bandpass slits were 10 nm on excitation and 5 nm on emission. Excitation wavelengths were 286 nm for tryptophan and 334 nm for pyrene. Pyrene emission spectra were recorded in a 350;–500 nm interval. Incubation of SPM with Aß1-40 was accomplished using procedures reported by our laboratory (16) (17). SPM were added to phosphate buffered saline (PBS: 137 mM NaCl, 2.7 mM KCl, 6.5 mM Na2HPO4, 1.5 mM KH2PO4, 20 mM HEPES, pH adjusted to 7.4 with Tris base) that was the control buffer or PBS containing 10-6 M Aß1-40, to give a final volume of 1 ml (50 µg of SPM protein/ml). Samples were incubated for 30 min in a thermostated water bath at 36.5°C with continuous shaking in darkness. The samples were then transferred to a 1 ml quartz cuvette and placed in a thermostated cuvette chamber. When the temperature was stable, endogenous tryptophans of SPM proteins were excited and fluorescence spectra was recorded in the wavelength interval 300;–400 nm. Next, 10-5 M of pyrene (1 µl of 10-2 M solution in dimethylformamide, 1 µl/min) was added. Pyrene was excited 1 min later through energy transfer from tryptophan (excitation wavelength 286 nm) and fluorescence emission spectra of pyrene were then recorded. Taking into account that the Forster radius (the energy transfer-limiting distance) for tryptophan-pyrene donor-acceptor pair is 3 nm (27), only pyrene located in annular lipid (close to proteins) was excited and the viscosity of annular lipid was considered proportional to the ratio Fe/Fm, where Fe and Fm are the fluorescence intensities of pyrene eximer (at 480 nm) and monomer (at 373 nm), respectively. Pyrene was then excited at 334 nm and fluidity of total or bulk lipid was considered proportional to the ratio Fe/Fm obtained with this excitation wavelength.

Total phospholipid and cholesterol content
Lipids were extracted using procedures described previously from our laboratory (24) (25). Samples were extracted in 2:1 chloroform;–methanol (v/v). The mixture was centrifuged at 2000 g for 10 min. The lower organic phase containing the lipids was filtered through a Pasteur pipet column packed with glass wool and anhydrous Na2SO4. The extracted lipids were then dried and brought up in l ml of chloroform. Total phospholipid phosphorous amounts in SPM of cerebral cortex, hippocampus, and cerebellum were quantified as previously described (28). SPM cholesterol of the three brain regions was determined enzymatically in a microassay using the Boehringer-Mannheim diagnostic kit (29) and procedures reported by our laboratory (26) (30) (31). The assay mixture was read at 490 nm in a microplate scanner (Molecular Devices, Sunnyvale, CA).

Student's t-tests were used for statistical analyses. All data are presented as means ± standard error of the mean (SEM).


  RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES

Annular fluidity
Excitation of pyrene by energy transfer from tryptophan residues of SPM proteins was used as an indicator of annular lipid fluidity. This method is a sensitive tool for examining behavior of amphipathic molecules in membranes (17) (22) (23) (26). It can be seen in Table 1 that the pyrene eximer/monomer ratio was significantly higher in cerebellar SPM as compared with SPM of cerebral cortex and hippocampus, indicating a more fluid environment in cerebellar SPM. The pyrene eximer /monomer ratio was significantly lower in hippocampal SPM as compared with the two other brain regions (Table 1).


 
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  		Table 1. Baseline annular fluidity and bulk fluidity of different brain regions of rat synaptic plasma membranes

Aß1-40 significantly increased annular fluidity in SPM of cerebral cortex (P <= 0.05) and hippocampus (P <= 0.001) as compared with control SPM ( Fig 1). However, annular fluidity of cerebellar SPM was unaffected by Aß1-40. The pyrene eximer/monomer ratios did not significantly differ between cerebellar control SPM and SPM incubated with Aß1-40 (Fig 1).



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  		Figure 1. Annular fluidity of SPM from hippocampus, cerebral cortex, and cerebellum, and effects of Aß1-40. SPM were incubated with Aß1-40 (10-6 M) at 36.5°C for 30 min. Annular fluidity was determined by using the eximer/monomer fluorescence ratio (Fe/Fm) for pyrene when pyrene was excited (286 nm) through energy transfer from SPM tryptophan residues as described in Materials and Methods. Values are means ± SEM (n = 4 SPM preparations). * P <= 0.001 as compared with hippocampal SPM control; ** P <= 0.05 as compared with SPM cerebral cortex control.

Bulk fluidity
Excimer formation of pyrene when the probe was excited at its excitation wavelength (334 nm) was used as indicator of bulk fluidity (17) (22) (23) (26). Baseline bulk fluidity of SPM differed among the three brain regions (Table 1). Cerebellar SPM were significantly most fluid, followed by SPM of the cerebral cortex and SPM of the hippocampus (P <= 0.001). Differences in bulk fluidity of SPM from cerebellum, cerebral cortex, and hippocampus are similar to differences observed for annular fluidity of the three brain areas. It is seen in Fig 2 that Aß1-40 significantly increased bulk fluidity of SPM from hippocampus (P <= 0.005) and SPM of the cerebral cortex (P <= 0.01). Bulk fluidity of SPM from the cerebellum was not altered by Aß1-40.



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  		Figure 2. Bulk fluidity of SPM from hippocampus, cerebral cortex, and cerebellum, and effects of Aß1-40. SPM were incubated with Aß1-40 (10-6 M) at 36.5°C for 30 min. The eximer/monomer fluorescence ratio (Fe/Fm) for pyrene when pyrene was excited at 334 nm was used as a measure of SPM bulk fluidity as described in Materials and Methods. Values are means ± SEM (n = 4 SPM preparations). * P <= 0.005 as compared with hippocampal SPM control; ** P <= 0.01 as compared with cerebral cortex SPM control.

SPM cholesterol and phospholipid amounts
Cholesterol is one of the major lipids in SPM and is an important contributor to membrane fluidity. SPM cholesterol content significantly differed among the three brain regions ( Table 2). SPM of cerebellum had significantly (P <= 0.008) less cholesterol as compared with SPM of cerebral cortex and SPM of the hippocampus. Taking cholesterol content in cerebellum SPM as 100%, we observed approximately 20% more cholesterol in hippocampal SPM and 13% more cholesterol in SPM of cerebral cortex. SPM total cholesterol amounts were inversely correlated with SPM annular fluidity (r = -0.990) and SPM bulk fluidity (r = -0.897). The more fluid SPM was associated with less cholesterol.


 
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  		Table 2. Total amounts of cholesterol and phospholipid in synaptic plasma membranes of different brain regions

Data in Table 2 show that the total amounts of SPM phospholipid differed among the three brain regions. There was significantly less phospholipid in SPM of cerebellum as compared with SPM of hippocampus (P <= 0.03) and SPM of cerebral cortex (P <= 0.001). There was approximately 23% and 16% less phospholipid in SPM of cerebellum as compared with hippocampal SPM and SPM of cerebral cortex, respectively. The cholesterol to phospholipid molar ratios did not significantly differ among SPM of cerebellum, hippocampus, and cerebral cortex.


  DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES

Aß is an amphipathic molecule that interacts with lipids. This interaction includes several functions, such as membrane perturbation (17) (19) (32), lipid binding, transport, and APP and Aß expression (15) (33) (34) (35) (36) (37). Cholesterol is a lipid that has been receiving increasing attention with respect to the dynamics of Aß [as reviewed in refs. (3), (10)]. The precise nature of the interaction between Aß and cholesterol is not well understood. This study tested the hypothesis that membrane perturbation induced by Aß would be associated with cholesterol content. Aß increased both annular fluidity and bulk fluidity of SPM from cerebral cortex and hippocampus. However, Aß had no effect on either annular or bulk fluidity of SPM from cerebellum. These differential effects of Aß on perturbation of SPM were associated with cholesterol content and brain region.

Energy transfer between tryptophan amino acid residues of SPM proteins and pyrene was used to determine annular fluidity, or the fluidity of the lipid environment in proximity to proteins. Bulk fluidity was measured in SPM using the fluorescence intensity of pyrene alone. The sensitivity of these techniques has been previously reported using SPM and different treatment conditions (17) (22) (23) (26). Annular fluidity and bulk fluidity differed among SPM of the three brain regions with fluidity of cerebellum > cortex > hippocampus. Aß had no effect on fluidity of cerebellar SPM. Aß1-40-induced increase in fluidity was greatest in hippocampal SPM, followed by SPM of cerebral cortex. It is well established that changes in membrane fluidity can alter protein function (38). For example, the magnitude of effects of Aß on SPM fluidity are comparable to effects of cholesterol oxidation on fluidity of SPM that resulted in a significant decrease in Ca2 + Mg2-ATPase activity (26). The effects of Aß1-40 on membrane fluidity are consistent with previous studies reporting Aß-induced increases in fluidity using energy transfer and pyrene (16) (17) and studies examining membrane structure using circular dichroism, Fourier transform infrared-polarized attenuated total reflection spectroscopy, and small angle X-ray diffraction (15) (16). There have been reports by other groups showing that Aß decreased fluidity of brain homogenates and liposomes using polarization and anisotropy of diphenylhexatriene (DPH) (19) (32) (39). Certainly technical differences among the various studies could contribute to the opposite effects of Aß on membranes. For example, pyrene and DPH are structurally different and such differences can influence their behavior (40) (41). Pyrene is spherical in structure and is positioned at the terminal end of the acyl groups. DPH is a rodlike structure whose axis is parallel to the acyl groups. Alternatively, it is becoming increasingly clear that cell membranes are vastly heterogenous with respect to lipid domains (42) (43) (44). Behavior of Aß in membranes may be dependent on its interaction with lipid domains as revealed by different biophysical techniques.

Aß-induced membrane perturbation was positively correlated with SPM cholesterol content. Effects of soluble Aß on membranes may involve the direct interaction of hydrophobic amino acid residues of Aß with the hydrophobic regions of cholesterol. This hypothesis is based on the following lines of evidence. Aß is an amphipathic molecule but it has been shown using X-ray diffraction that soluble Aß1-40 prefers the hydrophobic region of SPM (16). Aggregated Aß1-40, on the other hand, was positioned close to the polar headgroups of SPM and binds lipids in an aqueous environment (16) (33). NMR spectroscopy techniques showed that ethanol, another amphipathic molecule that also fluidizes membranes, binds to cholesterol but only in solvents with low dielectric constants (45). The hydrophobic lipid core of SPM has a dielectric of approximately 2 (46) making it a very hydrophobic environment and an environment that may be thermodynamically favorable for hydrophobic interaction of soluble Aß with cholesterol. Finally, ethanol (25 mM) increased annular fluidity and bulk fluidity of SPM from cerebral cortex (22) (23) similar to effects of Aß. Fluidity of SPM from cerebellum was unaffected by 100 mM ethanol (data not shown) as observed for effects of Aß. The interaction of Aß and cholesterol have been emphasized in this article. However, other lipids have been reported to be associated with Aß dynamics (15) (37) (47) (48).

Aß in the present study increased annular fluidity and bulk fluidity and these effects were related to SPM cholesterol content. Several studies have indicated that cholesterol content of cells may regulate APP and Aß processing (49) (50) (51) (52), and this processing may occur in microdomains such as lipid rafts and caveolae (11) (12) (13) (53). Both lipid rafts and caveolae are enriched in cholesterol. Two other domains of membranes are the exofacial and cytofacial membrane leaflets (54) (55) (56). Cholesterol is asymmetrically distributed in the two SPM leaflets with the cytofacial leaflet containing 85% of the total amount of SPM cholesterol. SPM cholesterol asymmetry has been reported to be altered in ethanol-tolerant mice, apoE-deficient mice, and aged mice (24) (25) (57). There was, for example, an approximately 2-fold increase in the exofacial leaflet cholesterol of 24- to 25-month-old mice as compared with 3- to 4-month-old mice (24). The total amount of SPM cholesterol did not differ in the two groups. The redistribution of cholesterol between the two leaflets could have two major consequences with respect to Aß activity. First, lipid raft or caveolae functions could be affected, which might act on APP and Aß processing. Secondly, the increase in cholesterol of the exofacial leaflet may act as a foundation for the accumulation of Aß and development of fibrillogenesis. Recent findings have shown that a unique Aß species catalyzes fibrillogenesis of soluble Aß and that this process was dependent on cholesterol (52) (58). It would appear that cholesterol accentuates the pathophysiology of Aß.


  FOOTNOTES

Abbreviations: AD, Alzheimer's disease; Aß, amyloid ß-peptide; APP, amyloid precursor protein; DPH, diphenylhexatriene; SPM, synaptic plasma membranes. Back


  ACKNOWLEDGMENTS

This work was supported by grants from the National Institutes of Health (AA-10806), Alzheimer's Association, and the Department of Veterans Affairs.

Manuscript received February 15, 2001; and in revised form April 10, 2001


  REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES

  1. Liu, Y., Peterson, D. A., Schubert, D. 1998. Amyloid ß peptide alters intracellular vesicle trafficking and cholesterol homeostasis. Proc. Natl. Acad. Sci. USA. 95:13266-13271[Abstract/Free Full Text].

  2. Sparks, D. L. 1997. Coronary artery disease, hypertension, apoE, and cholesterol: a link to Alzheimer's disease? Ann. NY Acad. Sci. 826:128-146[Abstract/Free Full Text].

  3. Wood, W. G., Schroeder, F., Avdulov, N. A., Chochina, S. V., Igbavboa, U. 1999. Recent advances in brain cholesterol dynamics: transport, domains and Alzheimer's disease. Lipids. 34:225-234[Medline].

  4. Jick, H., Zornberg, G. L., Jick, S. S., Seshadri, S., Drachman, D. A. 2000. Statins and the risk of dementia. Lancet. 356:1627-1631[Medline].

  5. Wolozin, B., Kellman, W., Ruosseau, P., Celesia, G. G., Siegel, G. 2000. Decreased prevalence of Alzheimer's disease associated with 3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitors. Arch. Neurol. 57:1439-1443[Abstract/Free Full Text].

  6. Strittmatter, W. J., Roses, A. D. 1996. Apolipoprotein E and Alzheimer's disease. Annu. Rev. Neurosci. 19:53-77[Medline].

  7. Weisgraber, K. H., Mahley, R. W. 1996. Human apolipoprotein E: the Alzheimer's disease connection. FASEB J. 10:1485-1494[Abstract].

  8. Poirier, J., Davignon, J., Bouthillier, D., Kogan, S., Bertrand, P., Gauthier, S. 1993. Apolipoprotein E polymorphism and Alzheimer's disease. Lancet. 342:697-699[Medline].

  9. Selkoe, D. J. 1994. Cell biology of the amyloid ß-protein precursor and the mechanism of Alzheimer's disease. Annu. Rev. Cell Biol. 10:373-403.

  10. Liu, Y. 1999. Understanding the biological activity of amyloid proteins in vitro: from inhibited cellular MTT reduction to altered cellular cholesterol homeostasis. Prog. Neuropsychopharmacol. Biol. Psychiatry. 23:377-395[Medline].

  11. Lee, S-J., Liyanage, U., Bickel, P. E., Xia, W., Lansbury, P. T., Kosik, K. S. 1998. A detergent-insoluble membrane compartment contains amyloid-beta in vivo. Nature Medicine. 4:730-734[Medline].

  12. Morishima-Kawashima, M., Ihara, Y. 1998. The presence of amyloid ß-protein in the detergent-insoluble membrane compartment of human neuroblastoma cells. Biochemistry. 37:15247-15253[Medline].

  13. Hayashi, H., Mizuno, T., Michikawa, M., Haass, C., Yanagisawa, K. 2000. Amyloid precursor protein in unique cholesterol-rich microdomains different from caveolae-like domains. Biochim. Biophys. Acta. 1483:81-90[Medline].

  14. Villalain, J. 1996. Location of cholesterol in model membranes by magic-angle-sample-spinning NMR. Eur. J. Biochem. 241:586-593[Medline].

  15. Matsuzaki, K., Horikiri, C. 1999. Interactions of amyloid ß-peptide (1;–40) with ganglioside-containing membranes. Biochemistry. 38:4137-4142[Medline].

  16. Mason, R. P., Jacob, R. F., Walter, M. F., Mason, P. E., Avdulov, N. A., Chochina, S. V., Igbavboa, U., Wood, W. G. 1999. Distribution and fluidizing action of soluble and aggregated amyloid beta-peptide in rat synaptic plasma membranes. J. Biol. Chem. 274:18801-18807[Abstract/Free Full Text].

  17. Avdulov, N. A., Chochina, S. V., Igbavboa, U., O'Hare, E. O., Schroeder, F., Cleary, J. P., Wood, W. G. 1997. Amyloid ß-peptides increase annular and bulk fluidity and induce lipid peroxidation in brain synaptic plasma membranes. J. Neurochem. 68:2086-2091[Medline].

  18. Müller, W. E., Koch, S., Eckert, A., Hartmann, H., Scheuer, K. 1995. ß-amyloid peptide decreases membrane fluidity. Brain Res. 674:133-136[Medline].

  19. Müller, W. E., Eckert, G. P., Scheuer, K., Cairns, N. J., Maras, A., Gattaz, W. F. 1997. Effects of ß-amyloid peptides on the fluidity of membranes from frontal and parietal lobes of human brain. High potencies of Aß 1;–42 and Aß 1;–43. Amyloid: Int. J. Exp. Clin. Invest. 5:10-15.

  20. Soderberg, M., Edlund, C., Kristensson, K., Dallner, G. 1990. Lipid compositions of different regions of the human brain during aging. J. Neurochem. 54:415-423[Medline].

  21. Svennerholm, L., Bostrom, K., Jungbjer, B., Olsson, L. 1994. Membrane lipids of adult human brain: lipid composition of frontal and temporal lobe in subjects of age 20 to 100 years. J. Neurochem. 63:1802-1811[Medline].

  22. Avdulov, N. A., Chochina, S. V., Draski, L., Deitrich, R. A., Wood, W. G. 1995. Chronic ethanol consumption alters effects of ethanol in vitro on brain membrane structure of HAS and LAS rats. Alcohol Clin. Exp. Res. 19:886-891[Medline].

  23. Avdulov, N. A., Wood, W. G., Harris, R. A. 1994. Effects of ethanol on structural parameters of rat brain membranes: relationship to genetic differences in ethanol sensitivity. Alcohol Clin. Exp. Res. 18:53-59[Medline].

  24. Igbavboa, U., Avdulov, N. A., Schroeder, F., Wood, W. G. 1996. Increasing age alters transbilayer fluidity and cholesterol asymmetry in synaptic plasma membranes of mice. J. Neurochem. 66:1717-1725[Medline].

  25. Igbavboa, U., Avdulov, N. A., Chochina, S. V., Wood, W. G. 1997. Transbilayer distribution of cholesterol is modified in brain synaptic plasma membranes of knockout mice deficient in the low density lipoprotein receptor, apolipoprotein E, or both proteins. J. Neurochem. 69:1661-1667[Medline].

  26. Wood, W. G., Igbavboa, U., Rao, A. M., Schroeder, F., Avdulov, N. A. 1995. Cholesterol oxidation reduces Ca2+ + Mg2+-ATPase activity, interdigitation, and increases fluidity of brain synaptic plasma membranes. Brain Res. 683:36-42[Medline].

  27. Tahara, Y., Murata, M., Ohnishi, S-I. 1992. Functional signal peptide reduces bilayer thickness of phosphatidylcholine liposomes. Biochemistry. 31:8747-8754[Medline].

  28. Bartlett, G. R. 1959. Phosphorous assay in columm chromatography. J. Biol. Chem. 234:466-468[Free Full Text].

  29. Auerbach, B. J., Parks, J. S., Applebaum-Bowden, D. 1990. A rapid and sensitive micro-assay for the enzymatic determination of plasma and lipoprotein cholesterol. J. Lipid Res. 30:738-742.

  30. Rao, A. M., Igbavboa, U., Semotuk, M., Schroeder, F., Wood, W. G. 1993. Kinetics and size of cholesterol lateral domains in synaptosomal membranes: modification by sphingomyelinase and effects on membrane enzyme activity. Neurochem. Int. 23:45-52[Medline].

  31. Wood, W. G., Rao, A. M., Igbavboa, U., Semotuk, M. 1993. Cholesterol exchange and lateral cholesterol pools in synaptosomal membranes of pair-fed control and chronic ethanol-treated mice. Alcohol Clin. Exp. Res. 17:345-350[Medline].

  32. Kremer, J. J., Pallitto, M. M., Sklansky, D. J., Murphy, R. M. 2000. Correlation of ß-amyloid aggregate size and hydrophobicity with decreased bilayer fluidity of model membranes. Biochemistry. 39:10309-10318[Medline].

  33. Avdulov, N. A., Chochina, S. V., Igbavboa, U., Vassiliev, A. V., Wood, W. G. 1997. Lipid binding to amyloid ß-peptide: preferential binding of cholesterol as compared with phosphatidylcholine and fatty acids. J. Neurochem. 69:1746-1752[Medline].

  34. Choo-Smith, L. P., Garzon-Rodriguez, W., Glabe, C. G., Surewicz, W. K. 1997. Acceleration of amyloid fibril formation by specific binding of Aß-(1;–40) peptide to ganglioside-containing membrane vesicles. J. Biol. Chem. 272:22987-22990[Abstract/Free Full Text].

  35. Koudinova, N. V., Berezov, T. T., Koudinov, A. R. 1996. Multiple inhibitory effects of Alzheimer's peptide Aß1;–40 on lipid biosynthesis in cultured human HepG2 cells. FEBS Lett. 395:204-206[Medline].

  36. Terzi, E., Holzemann, G., Seelig, J. 1994. Alzheimer beta-amyloid peptide 25;–35: electrostatic interactions with phospholipid membranes. Biochemistry. 33:7434-7441[Medline].

  37. Yanagisawa, K., Odaka, A., Suzuki, N., Ihara, Y. 1995. GM1 ganglioside-bound amyloid ß-protein (Aß): a possible form of preamyloid in Alzheimer's disease. Nature Medicine. 1:1062-1066[Medline].

  38. Lentz, B. R. 1988. Organization of membrane lipids by intrinsic membrane proteins. In Lipid Domains and the Relationship to Membrane Function. R. C. Aloia, C. C. Curtain, and L. M. Gordon, editors. Alan R. Liss, Inc., New York. 141;–161.

  39. Eckert, G. P., Cairns, N. J., Maras, A., Gattaz, W. F., Müller, W. E. 2000. Cholesterol modulates the membrane disordering effects of ß-amyloid peptides in the hippocampus: specific changes in Alzheimer's disease. Dement. Geriatr. Cogn. Disord. 11:181-186[Medline].

  40. Podo, F., Blasie, J. K. 1977. Nuclear magnetic resonance studies of lecithin bimolecular leaflets with incorporated fluorescent probes. Proc. Natl. Acad. Sci. USA. 74:1032-1036[Abstract/Free Full Text].

  41. Mulders, F., Van Langen, H., Van Ginkel, G., Levine, Y. K. 1986. The static and dynamic behaviour of fluorescent probe molecules in lipid bilayers. Biochim. Biophys. Acta. 859:209-218.

  42. Curtain, C. C., L. M. Gordon, and R. C. Aloia. 1988. Lipid domains in biological membranes: conceptual development and significance. In Lipid Domains and the Relationship to Membrane Function. R. C. Aloia, C. C. Curtain, and L. M. Gordon, editors. Alan R. Liss, Inc., New York. 1;–15.

  43. Schroeder, F., W. G. Wood, and A. B. Kier. 1998. The biological membrane and lipid domains. In Cell Physiology Source Book. N. Sperelakis, editor. Academic Press, San Diego, CA. 61;–74.

  44. Wood, W. G., A. M. Rao, F. Schroeder, and U. Igbavboa. 1993. Membrane cholesterol and ethanol: domains, kinetics, and protein function. In Alcohol, Cell Membranes, and Signal Transduction in Brain. C. Alling, I. Diamond, S. W. Leslie, G. Y. Sun, and W. G. Wood, editors. Plenum Press, New York. 13;–32.

  45. Daragan, V. A., Voloshin, A. M., Chochina, S. V., Khazanovich, T. N., Wood, W. G., Avdulov, N. A., Mayo, K. H. 2000. Specific binding of ethanol to cholesterol in organic solvents. Biophys. J. 79:406-415[Abstract/Free Full Text].

  46. Colles, S., Wood, W. G., Myers-Payne, S. C., Igbavboa, U., Avdulov, N. A., Joseph, J., Schroeder, F. 1995. Structure and polarity of mouse brain synaptic plasma membrane: effects of ethanol in vitro and in vivo. Biochemistry. 34:5945-5959[Medline].

  47. McLaurin, J., Chakrabartty, A. 1997. Characterization of the interactions of Alzheimer ß-amyloid peptides with phospholipid membranes. Eur. J. Biochem. 245:355-363[Medline].

  48. Terzi, E., Holzemann, G., Seelig, J. 1997. Interaction of Alzheimer beta-amyloid peptide (1;–40) with lipid membranes. Biochemistry. 36:14845-14852[Medline].

  49. Bodovitz, S., Klein, W. L. 1996. Cholesterol modulates {alpha}-secretase cleavage of amyloid precursor protein. J. Biol. Chem. 271:4436-4440[Abstract/Free Full Text].

  50. Howlands, D. S., Trusko, S. P., Savage, M. J., Reaume, A. G., Lang, D. M., Hirsch, J. D., Maeda, N., Siman, R., Greenberg, B. D., Scott, R. M., Flood, D. G. 1998. Modulation of secreted beta-amyloid precursor protein and amyloid beta peptide in brain by cholesterol. J. Biol. Chem. 273:16576-16582[Abstract/Free Full Text].

  51. Simons, M., Keller, P., Destrooper, B., Beyreuther, K., Dotti, C. G., Simons, K. 1998. Cholesterol depletion inhibits the generation of beta-amyloid in hippocampal neurons. Proc. Natl. Acad. Sci. USA. 95:6460-6464[Abstract/Free Full Text].

  52. Mizuno, T., Haass, C., Michikawa, M., Yanagisawa, K. 1998. Cholesterol-dependent generation of a unique amyloid ß-protein from apically missorted amyloid precursor protein in MDCK cells. Biochim. Biophys. Acta. 1373:119-130[Medline].

  53. Nishiyama, K., Trapp, B. D., Ikezu, T., Ransohoff, R. M., Tomita, T., Iwatsubo, T., Kanazawa, I., Hsiao, K. K., Lisanti, M. P., Okamoto, T. 1999. Caveolin-3 upregulation activates ß-secretase-mediated cleavage of the amyloid precursor protein in Alzheimer's disease. J. Neurosci. 19:6538-6548[Abstract/Free Full Text].

  54. Op den Kamp, J. A. F. 1979. Lipid asymmetry in membranes. Annu. Rev. Biochem. 48:47-71[Medline].

  55. Schroeder, F. 1984. Role of membrane lipid asymmetry in aging. Neurobiol. Aging. 5:323-333[Medline].

  56. Wood, W. G., and F. Schroeder. 1992. Membrane exofacial and cytofacial leaflets: a new approach to understanding how ethanol alters brain membranes. In Alcohol and Neurobiology: Receptors, Membranes, and Channels. R. R.Watson, editor. CRC Press, Boca Raton, FL. 161;–184.

  57. Wood, W. G., Schroeder, F., Hogy, L., Rao, A. M., Nemecz, G. 1990. Asymmetric distribution of a fluorescent sterol in synaptic plasma membranes: effects of chronic ethanol consumption. Biochim. Biophys. Acta. 1025:243-246[Medline].

  58. Mizuno, T., Nakata, M., Naiki, H., Michikawa, M., Wang, R., Haass, C., Yanagisawa, K. 1999. Cholesterol-dependent generation of a seedling amyloid ß-protein in cell culture. J. Biol. Chem. 274:15110-15114[Abstract/Free Full Text].


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