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Related Experiment Videos

Beta-secretase activity increases with aging in human, monkey, and mouse brain.

Hiroaki Fukumoto1, Douglas L Rosene, Mark B Moss

  • 1Department of Neurology, Alzheimer Disease Research Unit, Massachusetts General Hospital-East, Charlestown, Massachusetts 02129, USA.

The American Journal of Pathology
|January 27, 2004
PubMed
Summary

Aging increases beta-secretase (BACE) activity in the brain, leading to higher amyloid beta (A beta) accumulation. This age-related rise in BACE activity may contribute to Alzheimer's disease risk.

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Area of Science:

  • Neuroscience
  • Biochemistry
  • Aging Research

Background:

  • Amyloid beta (A beta) protein accumulation in the brain is a hallmark of aging and neurodegenerative diseases.
  • Beta-site amyloid precursor protein cleaving enzyme (BACE) is a key enzyme in A beta production.

Purpose of the Study:

  • To investigate the hypothesis that aging is associated with increased BACE activity in the brain.
  • To evaluate the relationship between aging, BACE activity, and A beta levels across different species.

Main Methods:

  • Assessed BACE activity, BACE protein levels, and formic acid-extractable A beta levels in young and old mice, monkeys, and human brains.
  • Compared these levels across different age groups and brain regions.

Main Results:

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  • Aging was associated with increased brain A beta levels in all cohorts.
  • BACE activity significantly increased with age in mouse, monkey, and human brains, irrespective of brain region.
  • BACE protein levels remained unchanged with age.

Conclusions:

  • Age-related increases in BACE activity contribute to elevated brain A beta production and accumulation.
  • This mechanism may predispose individuals to Alzheimer's disease.