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Dominant and differential deposition of distinct beta-amyloid peptide species, A beta N3(pE), in senile plaques

来源:Neuron. 1995 Feb;14(2):457-66. doi: 10.1016/0896-6273(95)90301-1.     510

【导读】:Donanemab是Eli Lilly礼来开发的抗Aβ单克隆IgG1抗体。目前已完成治疗阿尔茨海默症(AD)的3期临床试验。预计2023年底可获得美国FDA的批准。

T C Saido, T Iwatsubo, D M Mann, H Shimada, Y Ihara, S Kawashima



Abstract


We analyzed an amino-terminal modification of beta-amyloid (A beta) peptide in brain, using anti-A beta antibodies that distinguish distinct molecular species. Examination of cortical sections from 28 aged individuals with a wide range in senile plaque density revealed that a molecular species distinct from the standard A beta is deposited in the brain in a dominant and differential manner. This modified A beta peptide (A beta N3(pE)) starts at the 3rd aminoterminal residue of the standard A beta, glutamate, converted to pyroglutamate through intramolecular dehydration. Because plaques composed of A beta N3(pE) are present in equivalent or greater densities than those composed of standard A beta bearing the first amino-terminal residue (A beta N1) and because deposition of the former species appears to precede deposition of the latter, as confirmed with specimens from Down's syndrome patients, the processes involved in A beta N3(pE) production and retention may play an early and critical role in senile plaque formation.


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