Evidence for increased amyloid enhancing factor activity in Alzheimer brain extract

Area of Science:

• Neuroscience
• Biochemistry

Background:

• Alzheimer's disease is a progressive neurological disorder.
• Amyloid-beta plaques are a hallmark of Alzheimer's disease.
• Amyloid Enhancing Factor (AEF) is implicated in amyloid plaque formation.

Purpose of the Study:

• To investigate the presence and characteristics of AEF in human Alzheimer's disease brain samples.
• To determine if AEF activity differs between amyloid-positive and amyloid-negative brain tissues.

Main Methods:

• Human brain extracts (normal, Alzheimer's, Down's syndrome) were assayed for AEF activity using a mouse bioassay.
• AEF-positive fractions were subjected to dialysis, gel filtration, and SDS-PAGE.
• The effect of phenylmethylsulfonyl fluoride (PMSF) on AEF activity was evaluated.

Main Results:

• AEF activity was detected in five of seven amyloid-positive Alzheimer's brain extracts at a low protein dosage.
• Marginal AEF activity was found in normal brain extracts at higher dosages.
• The active AEF fraction contained peptides between 14 and 66 kDa and its activity was abolished by PMSF.

Conclusions:

• Alzheimer's disease brain samples exhibit higher AEF concentrations compared to normal or amyloid-negative tissues.
• Alzheimer's-associated AEF appears to be a serine/thiol proteinase.
• This study provides the first evidence of AEF activity in Alzheimer's disease brain samples.