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Human brain beta A4 amyloid protein precursor of Alzheimer's disease: purification and partial characterization
R D Moir1, R N Martins, A I Bush
1Department of Pathology, University of Melbourne, Parkville, Australia.
Abstract:
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.
Insights
Researchers purified amyloid precursor protein (APP) from human brain, finding truncated soluble forms. This purification aids in understanding Alzheimer's disease and APP's role.
Area of Science:
- Neuroscience
- Biochemistry
Background:
- Alzheimer's disease is characterized by amyloid deposition.
- Beta A4 protein, a major component, is derived from amyloid precursor protein (APP).
Purpose of the Study:
- To describe a procedure for the complete purification of APP from human brain.
- To investigate the forms and processing of APP in relation to Alzheimer's disease.
Main Methods:
- Purification of APP from human brain.
- Amino terminal sequencing of APP.
- Identification of APP molecular masses using gel electrophoresis.
- Immunoprecipitation with carboxyl terminus-directed antibodies.
Main Results:
- A procedure for complete APP purification from human brain was established.
- Two major APP forms (100-110 kDa and 120-130 kDa) were identified.
- Soluble APP forms were found to be truncated, and carboxyl terminus truncation also occurred during postmortem autolysis.
Conclusions:
- Purified human brain APP is now available for further study.
- This resource will help investigate APP's normal function.
- Understanding APP cleavage is crucial for Alzheimer's disease research.