Neurotoxicity and physicochemical properties of Abeta mutant peptides from cerebral amyloid angiopathy: implication for the pathogenesis of cerebral amyloid angiopathy and Alzheimer's disease.

[hereditary cerebral hemorrhage with amyloidosis]

Cerebral amyloid angiopathy (CAA ) due to beta -amyloid (Abeta ) is one of the specific pathological features of familial Alzheimer 's disease . Abeta mainly consisting of 40 - and 42 -mer peptides (Abeta 40 and Abeta 42 ) exhibits neurotoxicity and aggregative abilities . All of the variants of Abeta 40 and Abeta 42 found in CAA were synthesized in a highly pure form and examined for neurotoxicity in PC 12 cells and aggregative ability . All of the Abeta 40 mutants at positions 22 and 23 showed stronger neurotoxicity than wild-type Abeta 40 . Similar tendency was observed for Abeta 42 mutants at positions 22 and 23 whose neurotoxicity was 50 -200 times stronger than that of the corresponding Abeta 40 mutants , suggesting that these Abeta 42 mutants are mainly involved in the pathogenesis of CAA . Although the aggregation of E 22 G -Abeta 42 and D 23 N -Abeta 42 was similar to that of wild-type Abeta 42 , E 22 Q-Abeta 42 and E 22 K -Abeta 42 aggregated extensively , supporting the clinical evidence that Dutch and Italian patients are diagnosed as hereditary cerebral hemorrhage with amyloidosis . In contrast , A 21 G mutation needs alternative explanation with the exception of physicochemical properties of Abeta mutants . Attenuated total reflection-Fourier transform infrared spectroscopy spectra suggested that beta -sheet content of the Abeta mutants correlates with their aggregation . However , beta -turn is also a critical secondary structure because residues at positions 22 and 23 that preferably form two -residue beta -turn significantly enhanced the aggregative ability .

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Diseases presenting "examined for neurotoxicity in pc12 cells and aggregative ability" symptom

hereditary cerebral hemorrhage with amyloidosis

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