Alzheimer's disease and Down syndrome: leukocyte membrane fluidity alterations

Down Syndrome (DS) patients over the age of 40 have brain lesions identical to those of patients with Alzheimer's Disease (AD). We have earlier shown that with some membrane probes, the plasma membranes of circulating leukocytes had increased fluidity in AD compared to the normally more rigid membranes in similarly aged subjects. We next questioned whether the occurrence of AD-like pathological lesions in older DS subjects would be associated with a similar increase in membrane fluidity. Fluidity was assessed by measurements of steady-state fluorescence anisotropy using TMA-DPH, which anchors at the plasma membrane surface, and a series of 9-anthroyloxy fatty acids substituted with the fluorescent moiety at different positions on the fatty acid, which permit measurement of fluidity at different depths of the plasma membrane. This was done simultaneously in neutrophils, lymphocytes, and monocytes utilizing flow cytometry. In older DS subjects (average age 52.6), plasma membrane fluidity was indeed increased, a finding similar to that with AD leukocytes. Membrane fluidity of leukocytes of young DS subjects (average age 23.6 years) was less than that seen in older subjects. Membrane changes may result from lipophilic substances released from the central nervous system, or may reflect intrinsic differences in membrane structure unique in DS.