Amyloid β protein (Aβ) deposition: Aβ42(43) precedes Aβ40 in down Syndrome

Abstract

The chronological relationship regarding deposition of amyloid β protein (Aβ) species, Aβ40 and Aβ42(43), was investigated in 16 brains from Down syndrome patients aged 31 to 64 years. The frontal cortex was probed with two end‐specific monoclonals that recognize Aβ40 or Aβ42(43). All senile plaques detected with an authentic β monoclonal were also Aβ42(43) positive, but only a varying proportion was Aβ40 positive. In young (≤ 50 years old) brains there were many Aβ42(43)‐positive, Aβ40‐negative diffuse plaques, but only few Aβ40‐positive senile plaques (mean, 6.3% of total number of senile plaques). The 2 youngest Down syndrome brains showed only diffuse plaques that were all Aβ42(43) positive but Aβ40 negative. Old (≤ 50 years old) brains contained many mature senile plaques with amyloid cores in addition to diffuse and immature plaques and the proportion of Aβ40‐positive senile plaques was increased (mean, 42% of total). Cerebral amyloid angiopathy was more abundant in old Down syndrome brains and was positive for both Aβ40 and Aβ42(43). In cerebral amyloid angiopathy, Aβ40 predominated over Aβ42(43) in both staining intensity and number of positive vessels. These results indicate that (1) the Aβ species intially deposited in the brain as senile plaques is Aβ42(43) and Aβ40 only appears a decade later, and (2) in cerebral amyloid angiopathy Aβ40 appears as early as Aβ42(43).