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

In Down syndrome (DS) brain an early, selective accumulation of amyloid β (Aβ) peptides ending at residue 42 (Aβ42) occurs. Whether this event depends on an altered processing of amyloid beta precursor prorein (APP) or on defective clearance is uncertain. To investigate this issue, we measured Aβ species 40 and 42 in plasma from 61 patients with DS, 77 age-matched normal controls, and 55 mentally retarded subjects without chromosomal abnormalities. The Aβ 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 Aβ species were significantly elevated in DS compared to control groups, and the extent of their increase reflects that expected from APP gene overexpression. Plasma levels of Aβ 40 and 42 did not correlate with apoE genotypes in DS and control cases, and with the extent of mental retardation in DS subjects. The results indicate that accumulation and clearance of plasma and cerebral Aβ are regulated by different and independent factors.