LYMPHOCYTE CONTENT OF AMYLOID PRECURSOR PROTEIN IS INCREASED IN DOWNS-SYNDROME AND AGING

We quantified cellular amyloid precursor protein (APP) in ethanol-perm eabilized peripheral lymphocytes from 13 subjects with Alzheimer's dis ease (AD), 11 subjects with Down's syndrome (DS), and 13 healthy elder ly and 31 healthy young controls. APP content was analyzed by indirect immunofluorescence and now cytometry, using the 22C11 monoclonal anti body (mAb) directed against an N-terminal domain of APP. Authenticity of 22C11 APP signal was confirmed by immunoblotting and flow cytometry studies with the mAb 6E10, directed against the A beta domain of APP. Consistent with gene dosage, patients with DS had 1.51-fold higher ly mphocyte APP signal than age-matched normal young subjects (corrected p < 0.05). Both AD patients and elderly control groups had significant ly increased lymphocyte APP signal compared to young controls (either comparison corrected p < 0.01). Indeed, increasing age in non-DS subje cts was significantly correlated with lymphocyte APP (r = 0.508, p < 0 .0001), such that APP immunoreactivity more than doubled from 20 to 80 years. Lymphocyte APP was nonsignificantly higher in AD vs. aged cont rols in this small sample. Increased cellular APP content in DS and ag ing may correspond to generalized alterations in expression or process ing of this molecule, and suggests a novel determinant for the timing of AD onset. Copyright (C) 1996 Elsevier Science Inc.