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E. Peiretti, C. Norfo, C. Abete, M. Palmas, C. Zaru, S. Dessì, M. Fossarello; Cholesterol Homeostasis is Altered in Peripheral Blood Mononuclear Cell (PBMCs) From Patients With Age-Related Macular Degeneration (AMD). Invest. Ophthalmol. Vis. Sci. 2008;49(13):3408.
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It is believed that drusen may signal the presence of an altered pathophysiology of the retinal pigment epithelium in patients with age-related macular degeneration (AMD). Recent evidence suggests that drusen formation and AMD share some similarities with β-amyloid (Aβ) diseases such as Alzheimer disease (AD). It has been demonstrated that Aβ deposition is specific to drusen in AMD and that Aβ assemblies are most prevalent in eyes with moderate high drusen loads, suggesting that Aβ might be associated with the more advanced stages of AMD. Supported by other studies showing that AD patients present modifications in cholesterol ester formations in brain and in peripheral cells, we analysed cholesterol metabolism in plasma and in peripheral blood mononuclear cells (PBMCs) from patients affected by AMD.
We evaluated lipoprotein profile in plasma and cholesterol esters in PBMCs from 56 patients with AMD, 61 patients with AD, 24 normal elderly controls and 84 young-middle age blood donors.
No significant differences in plasma total cholesterol levels emerged between the four groups, although patients with AD and AMD had a tendency to lower levels of high-density lipoprotein cholesterol than controls.However, quantitative analysis with oil-O red (ORO) staining performed on samples from patients and controls indicated a significant increase of neutral lipid levels (mainly cholesterol esters) in AMD and AD PBMCs in comparison with non-AMD and non-AD cells. The intensity of ORO staining in PBMCs of AD patients was significantly and directly correlated with the severity of cognitive alteration, determined by the Mini Mental (MMSE) scores. Similarly, the intensity of ORO staining in PBMCs from AMD patients was correlated with the severity of clinical signs .
These results are in agreement with several studies showing altered cholesterol homeostasis in patients with AD. We suggest that abnormal cholesterol esterification could represent a phenotype predisposing to the development of pathological process involving abnormal activation, and/or trafficking of membrane resident proteins such as amyloid precursor protein (APP) and β-secretase responsible for Aβ formation. Thus, cholesterol ester inhibition may be a way to control progression of such diseases.
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