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Is Alzheimer's disease a disorder of mitochondria-associated membranes?

Eric A Schon1, Estela Area-Gomez

  • 1Department of Neurology, Columbia University Medical Center, New York, NY, USA. eas3@columbia.edu

Journal of Alzheimer'S Disease : JAD
|April 28, 2010
PubMed

Insights

Presenilin proteins (PS1 and PS2) are found in mitochondria-associated membranes (MAM), crucial for Alzheimer's disease (AD) pathogenesis. Dysfunction in MAM explains various AD features beyond amyloid-beta and tau.

Area of Science:

  • Cell Biology
  • Neuroscience
  • Biochemistry

Background:

  • The subcellular localization of presenilin-1 (PS1) and presenilin-2 (PS2) in Alzheimer's disease (AD) pathogenesis is debated.
  • PS1 and PS2 mutations are linked to familial forms of AD.

Purpose of the Study:

  • To determine the predominant subcellular location of PS1 and PS2.
  • To investigate the role of presenilins in mitochondria-associated membranes (MAM) and their connection to AD pathology.

Main Methods:

  • Subcellular localization studies of PS1, PS2, and gamma-secretase activity.
  • Analysis of MAM function in relation to AD hallmarks.

Main Results:

  • Mitochondria-associated membranes (MAM) are identified as the primary location for PS1, PS2, and gamma-secretase.
  • Presenilins are hypothesized to maintain MAM function, crucial for lipid metabolism and calcium homeostasis.

Conclusions:

  • Compromised MAM function due to presenilin dysfunction may explain diverse AD features, including metabolic and calcium homeostasis alterations.
  • This finding offers a unifying hypothesis for both sporadic and familial Alzheimer's disease, potentially guiding new research directions.

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