Abstract
Amyloid β-protein (Aβ) accumulation in brain is thought to be important in causing the neuropathology of Alzheimer's disease (AD). Aβ interactions with both neurons and microglial cells play key roles in AD. Since vascular deposition of Aβ is also implicated in AD, the interaction of red cells with these toxic aggregates gains importance. However, the effects of Aβ interactions with red blood cells are less well understood. Synthetic amyloid β-protein (1-40) was labeled with biotin and preincubated at 37 °C for 4, 14 and 72 h to produce fibrils. Flow cytometry was used to study the binding of these fibrils to red cells. The amyloid fibrils had a high affinity for the red cell with increased binding for the larger fibrils produced by longer preincubation. Bovine serum albumin (BSA) did not reverse the binding, but actually resulted in a more efficient binding of the Aβ fibrils to the red cells. The interaction of Aβ with red cells increased the mean cell volume and caused the cells to become more spherical. This effect was greater for the longer fibrils. At the same time the interaction of Aβ with red cells produced an increase in their fluorescence measured after 16-h incubation at 37 °C. This increase in fluorescence is attributed to the formation of fluorescent heme degradation products. The effect of prior hemoglobin oxidation, catalase inhibition and glutathione peroxidase inhibition indicated that the amyloid-induced oxidative damage to the red cell involved hydrogen peroxide-induced heme degradation. These results suggest that amyloid interactions with the red cell may contribute to the pathology of AD.
Original language | English (US) |
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Pages (from-to) | 20-28 |
Number of pages | 9 |
Journal | Biochimica et Biophysica Acta - General Subjects |
Volume | 1622 |
Issue number | 1 |
DOIs | |
State | Published - Jun 20 2003 |
Externally published | Yes |
Keywords
- Amyloid fibril
- Biotin
- Flow cytometry
- Membrane
- Oxidative stress
- Red cell
ASJC Scopus subject areas
- Biophysics
- Biochemistry
- Molecular Biology