HUMAN BRAIN-BETA-A4 AMYLOID PROTEIN-PRECURSOR OF ALZHEIMERS-DISEASE - PURIFICATION AND PARTIAL CHARACTERIZATION

被引:52
作者
MOIR, RD
MARTINS, RN
BUSH, AI
SMALL, DH
MILWARD, EA
RUMBLE, BA
MULTHAUP, G
BEYREUTHER, K
MASTERS, CL
机构
[1] UNIV MELBOURNE,DEPT PATHOL,PARKVILLE,VIC 3052,AUSTRALIA
[2] MENTAL HLTH RES INST VICTORIA,PARKVILLE,AUSTRALIA
[3] UNIV HEIDELBERG,CTR MOLEC BIOL,W-6900 HEIDELBERG,GERMANY
关键词
AMYLOID PROTEIN PRECURSOR; BETA-A4; AMYLOID; ALZHEIMERS DISEASE; POSTMORTEM DEGRADATION; PROTEIN SEQUENCE; PROTEOLYSIS; MEMBRANE PROTEIN;
D O I
10.1111/j.1471-4159.1992.tb08465.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The major component of the amyloid deposition that characterizes Alzheimer's disease is the 4-kDa beta-A4 protein, which is derived from a much larger amyloid protein precursor (APP). A procedure for the complete purification of APP from human brain is described. The same amino terminal sequence of APP was found in two patients with Alzheimer's disease and one control subject. Two major forms of APP were identified in human brain with apparent molecular masses of 100-110 kDa and 120-130 kDa. Soluble and membrane fractions of brain contained nearly equal amounts of APP in both humans and rats. Immunoprecipitation with carboxyl terminus-directed antibodies indicates that the soluble forms of APP are truncated. Carboxyl terminus truncation of membrane-associated forms of human brain APP was also found to occur during postmortem autolysis. The availability of purified human brain APP will facilitate the investigation of its normal function and the events that lead to its abnormal cleavage in patients with Alzheimer's disease.
引用
收藏
页码:1490 / 1498
页数:9
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