Synthesis, aggregation, neurotoxicity, and secondary structure of various A beta 1-42 mutants of familial Alzheimer's disease at positions 21-23.

[hereditary cerebral hemorrhage with amyloidosis]

Cerebral amyloid angiopathy (CAA ) due to amyloid beta (A beta ) deposition is a key pathological feature of Alzheimer 's disease (AD ), especially in some form of familial Alzheimer 's disease (FAD ) including hereditary cerebral hemorrhage with amyloidosis -Dutch type . A beta mainly consists of 40 - and 42 -mer peptides (Abeta 1 -40 and A beta 1 -42 ), which accumulate in senile plaques of AD brains and show neurotoxicity for cultured nerve cells . We synthesized all variant forms of A beta 1 -42 associated with reported FAD , such as A 21 G (Flemish ), E 22 Q (Dutch ), E 22 K (Italian ), E 22 G (Arctic ), and D 23 N (Iowa ) along with three potential mutants by one point missense mutation (E 22 A , E 22 D , and E 22 V ) in a highly pure form , and examined their ability to aggregate and their neurotoxicity in PC 12 cells . The mutants at positions 22 and 23 showed potent aggregative ability and neurotoxicity whereas the potential mutants did not , indicating that A beta 1 -42 mutants at positions 22 and 23 play a critical role in FAD of Dutch -, Italian -, Arctic -, and Iowa -types . However , Flemish-type FAD needs alternative explanation except the aggregation and neurotoxicity of the corresponding A beta 1 -42 mutant .

Diseases
Validation

Diseases presenting "potent aggregative ability" symptom

hereditary cerebral hemorrhage with amyloidosis

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