Plasma levels of amyloid beta 40 and 42 are independent from ApoE genotypeand mental retardation in Down syndrome

In Down syndrome (DS) brain an early, selective accumulation of amyloid bet a (A beta) peptides ending at residue 42 (A beta 42) occurs. Whether this e vent depends on an altered processing of amyloid beta precursor protein (AP P) or on defective clearance is uncertain. To investigate this issue, we me asured A beta species 40 and 42 in plasma from 61 patients with DS, 77 age- matched normal controls, and 55 mentally retarded subjects without chromoso mal abnormalities. The A beta 40 and 42 plasma levels were then correlated with apolipoprotein E (apoE) genotypes in all groups of cases, and with I.Q . and Mini Mental Status Examination values in DS subjects. Both A beta spe cies were significantly elevated in DS compared to control groups, and the extent of their increase reflects that expected from APP gene overexpressio n. Plasma levels of A beta 40 and 42 did not correlate with apoE genotypes in DS and control cases, and with the extent of mental retardation in DS su bjects, The results indicate that accumulation and clearance of plasma and cerebral A beta are regulated by different and independent factors. Am. J, Med, Genet, 95:224-228, 2000, (C) 2000 Wiley-Liss, Inc.