Platelet membrane abnormality in Alzheimer's disease

Abstract

Fluorescence studies of membrane fluidity were conducted double-blind using platelet and red cell membranes prepared from 24 demented patients with probable Alzheimer's disease and 36 neurologically healthy subjects. The fluidity of the hydrocarbon and lipid-aqueous interface regions of cell membranes was determined at 37 degrees C by fluorescence spectroscopy using the lipid probes 1,6-diphenyl-1,3,5-hexatriene (DPH) and 1-[4-(trimethylamino)phenyl]-6-phenyl-1,3,5-hexatriene (TMA-DPH), respectively. The rotation rate of TMA-DPH in labeled platelet membranes did not differ between the groups. In contrast, the rotation rate of DPH in labeled platelet membranes from the demented patients (2.15 +/- 0.24 X 10(8)/sec, SD) was greater than that for the normal controls (1.93 +/- 0.13 X 10(8)/sec, SD, p = 3.8 X 10(-5)). This difference was reflected by a reduction in the steady-state anisotropy of DPH in labeled platelets from the demented group (0.1887 +/- 0.0085, SD) when compared to the respective mean for the controls (0.2000 +/- 0.0060, SD; p = 1.3 X 10(-7)). Abnormal membrane fluidity was significantly correlated with severity of dementia, but not with duration of illness or apparent age of onset. The findings do not support the hypothesis that Alzheimer's disease results from a pathological acceleration of the normal aging process, since normal aging is associated with decreased fluidity of cell membranes from platelets, as well as from lymphocytes, hepatocytes, and neurons.

Platelet membrane fluidity, family history, severity and age of onset in Alzheimer's disease

“…The significance of this finding is not fully understood. However, Zubenko et al (1987a) report that the group of AD patients with increased platelet membrane fluidity suffer from earlier onset of symptoms and their illness is more rapidly progressive. Zubenko et al (1988) reported that AD patients with raised platelet membrane fluidity had more first-degree relatives with the condition compared with those who had normal platelet membrane fluidity.…”

“…Our group has confirmed this (Hicks et a/., 1987) and shown that in this respect A D patients differ from cases of multi-infarct dementia, in which slight but not significant changes are found. Platelet membrane fluidity is not altered in mania or depression (Zubenko et a/., 1987a).…”

“…A threshold for DPH anisotropy of 0.1920 at 37°C (90-95th percentile for healthy elderly controls, Zubenko et al, 1987a) divides patients with AD 0885-6230 '901060395-06$05.00 0 1990 by John Wiley & Sons, Ltd.…”

Monozygotic twins concordant for probable Alzheimer disease and increased platelet membrane fluidity

“…Initial assessments of the specificity of this platelet membrane characteristic are promising. The increase in platelet membrane fluidity associated with Alzheimer disease was not found in platelets from patients with depression [Zubenko et al, 1987d], a common cause of reversible dementia in the elderly; mania [Zubenko and Cohen, 19851, which may also be accompanied by a secondary dementia; or multi-infarct dementia [Hicks et al, 19871. Several lines of evidence have suggested that the platelet membrane abnormality may result from a dysregulation in the biogenesis or turnover of internal membranes [Zubenko et a]., 1987c, f].…”

Clinical Diagnosis of Alzheimer's Disease

“…The authors concluded that they had discovered a biological subtype of AD. AD patients with the abnormality have an earlier age of onset and deteriorate more rapidly than those without [7], Zubenko and Teply [8] assessed PMF in 15 patients and 10 controls over a 12-month period. No significant changes took place in individual subjects suggesting that it was a stable biological marker.…”