Enhanced pathologic properties of Dutch-type mutant amyloid beta-protein.

[hereditary cerebral hemorrhage with amyloidosis]

Cerebrovascular amyloid beta -protein (Abeta ) deposition is a pathological feature of several related disorders including Alzheimer disease and hereditary cerebral hemorrhage with amyloidosis Dutch -type (HCHWA-D ). HCHWA-D is caused by a point mutation in the gene that encodes the Abeta precursor and results in a Glu --> Gln substitution at position 22 of Abeta . In comparison to Alzheimer disease , the cerebrovascular Abeta deposition in HCHWA-D is generally more severe , often resulting in intracerebral hemorrhage when patients reach 50 years of age . We recently reported that Abeta (1 -42 ), but not the shorter Abeta (1 -40 ) induces pathologic responses in cultured human leptomeningeal smooth muscle cells including cellular degeneration that is accompanied by a marked increase in the levels of cellular Abeta precursor and soluble Abeta peptide . In the present study , we show that the HCHWA-D mutation converts the normally nonpathologic Abeta (1 -40 ) into a highly pathologic form of the peptide for cultured human leptomeningeal smooth muscle cells . These findings suggest that these altered functional properties of HCHWA-D mutated Abeta may contribute to the early and often severe cerebrovascular pathology that is the hallmark of this disorder .

Diseases
Validation

Diseases presenting "a point mutation in the gene that encodes the abeta precursor" symptom

hereditary cerebral hemorrhage with amyloidosis

You can validate or delete this automatically detected symptom