Spin label and biochemical studies of erythrocyte membranes in Alzheimer's disease

Markesbery, William R.; Leung, Patrick K.; Butterfield, D. Allan

doi:10.1016/0022-510x(80)90175-6

Cited by 68 publications

(23 citation statements)

References 28 publications

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“…Ethical considerations, the lack of an animal model, and the limitations of current in vivo biochemical approaches confine neurochemical and diagnostic studies primarily to autopsy brain material. Abnormalities attributed to Alzheimer disease have been reported in peripheral tissues (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12), supporting the hypothesis that this may be a systemic disorder with the most prominent pathology in the central nervous system. Furthermore, the presence of Alzheimer-like neuropathology in older individuals with chromosome-21 trisomy (Down syndrome) (13), and the increased risk of developing the disease that first-degree relatives of Alzheimer patients have (14) raises the possibility of a genetic component of Alzheimer disease.…”

supporting

confidence: 53%

“…Therefore, the cell's genetic endowment should be the primary experimental variable (41,42). Despite the major pathological findings in the central nervous system of Alzheimer patients, the present study, as well as previous ones (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12), indicate that metabolic deficits occur in nonneuronal tissues. Cultured skin fibroblasts were seeded in sterilized glass scintillation vials (30,000 cells per vial) on day 0 and treated thereafter as described.…”

Section: Resultsmentioning

confidence: 65%

See 1 more Smart Citation

Alterations in calcium content and biochemical processes in cultured skin fibroblasts from aged and Alzheimer donors.

Peterson¹,

Goldman²

1986

Proc. Natl. Acad. Sci. U.S.A.

184

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Aging and Alzheimer disease lead to alterations in several biochemical properties of cultured skin fibroblasts. Total bound calcium increases in fibroblasts due to normal aging (+52%) and is elevated even further with Alzheimer disease (+197%). Processes that require mitochondrial function, such as glucose and glutamine oxidation, declined in cells from aged donors (-25%) and decreased even further in Alzheimer disease (-46%). In addition, biosynthetic processes that depend upon mitochondrial function, such as glucose or glutamine incorporation into protein and lipid, paralleled the oxidative decreases. Cytosolic and nuclear processes such as leucine incorporation into protein and thymidine into DNA were depressed more by aging than Alzheimer disease. These findings suggest that calcium homeostasis and mitochondrial functions are altered more by Alzheimer disease than normal aging.

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supporting

confidence: 53%

Section: Resultsmentioning

confidence: 65%

Alterations in calcium content and biochemical processes in cultured skin fibroblasts from aged and Alzheimer donors.

Peterson¹,

Goldman²

1986

Proc. Natl. Acad. Sci. U.S.A.

184

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“…2). Similar to our findings on neuronal (glyco)proteins in membrane prep arations of neocortex areas [49], we could detect no alterations in erythrocyte mem brane proteins of Alzheimer patients either with general protein stains or with anti bodies to glycophorin and band 4.1 [39], The latter findings confirm the data of Markesbery et al [79], who found no gross changes in membrane proteins, a normal rotational correlation time of spin-labeled sialic acid [80] and normal fluidity of erythrocyte membranes from Alzheimer patients [79]. These data suggest that increased membrane protein breakdown in the erythrocytes of Alzheimer patients is restricted to band 3.…”

Section: Bandsupporting

confidence: 82%

Alzheimer’s Disease and Cellular Aging: Membrane-Related Events as Clues to Primary Mechanisms

Bosman

Bartholomeus

Grip³

1991

Gerontology

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A fast-increasing number of data indicate that Alzheimer’s disease is a systemic disease, not restricted to the central nervous system. The nature of Alzheimer-related changes in peripheral cells confirms and emphasizes indications from biochemical and morphological studies in brain for the involvement of cellular membranes in this disease. Analysis of membrane changes in erythrocytes from Alzheimer patients suggests that the normal aging process of these cells is disturbed. These conclusions may form the basis for further studies leading to a better insight into the etiology of Alzheimer’s disease and to the development of diagnostic tools.

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“…Based on our observations and previously published data, (23)(24)(25)(26)(27)(28) can be rationalized as discreet ramifications of long-term oxidative stress. Further, our proposed scheme allows the possibility of radical-promoted, protease-independent or protease-dependent cleavage ofamyloid precursor protein at a site within the lipid bilayer.…”

Section: Discussionmentioning

confidence: 99%

“…4C). In contrast to the PBS buffer, an amyloid-derived signal did not appear in Hepes/PBN until [12][13][14][15][16][17][18][19][20][21][22][23][24] P35-25, 1825-35(scram), and BSA Spin Trapping. In a preliminary effort to assess the relationship between free radical production and peptide structure, we studied the reverse and scrambled analogues of ,B25-35, which are not neurotoxic (4).…”

mentioning

confidence: 99%

A model for beta-amyloid aggregation and neurotoxicity based on free radical generation by the peptide: relevance to Alzheimer disease.

Hensley

Carney

Mattson

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

1,029

718

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ABSTRACT-Amylold is a 39-to 43-amino-add neurotoxic peptide that aggregtes to form the core of Ahemer disease-sociated senile (amyloid) plaques. No EPR Spectrscopy and Spin Trapping. 8APs were solubilized to 1.0 mg/ml by addition of buffer [150 mM phosphatebuffered saline at pH 7.4 (PBS) or Hepes at pH 7.4] to lyophilized powder. BSA was solubilized similarly, to concentrations of 1-62 mg/ml. Buffer used for spin trapping contained 50 mM N-tert-butyl-a-phenylnitrone (PBN) (Sigma or Aldrich). In studies designed to inhibit putative metalcatalyzed reactions, the chelator deferoxamine mesylate or EDTA (Sigma) was dissolved to 10 mM in PBS/PBN prior to peptide addition. In a further attempt to nullify buffer-borne metals, PBS/PBN was stirred overnight with Chelex 100, a nonspecific metal-chelating agent.Peptide solutions were aliquoted into a 300-A4 aqueous quartz EPR flat cell that was subsequently sealed at both ends and immersed in a 3rC water bath for 0-135 hr and removed periodically for EPR analysis. EPR spectra were acquired on a Bruker (Billerica, MA) 300 EPR spectrometer equipped with computerized data acquisition software. Instrumental parameters were microwave power = 20 mW, modulation amplitude = 0.% G, gain = 1 x i1W, and conversion time =

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Spin label and biochemical studies of erythrocyte membranes in Alzheimer's disease

Cited by 68 publications

References 28 publications

Alterations in calcium content and biochemical processes in cultured skin fibroblasts from aged and Alzheimer donors.

Alterations in calcium content and biochemical processes in cultured skin fibroblasts from aged and Alzheimer donors.

Alzheimer’s Disease and Cellular Aging: Membrane-Related Events as Clues to Primary Mechanisms

A model for beta-amyloid aggregation and neurotoxicity based on free radical generation by the peptide: relevance to Alzheimer disease.

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