Columbia University Medical Center

Clue to Cause of Alzheimer’s Disease Found in Mitochondria “Bridges”

Lipid droplets (green dots) are deposited in skin cells from AD patients.These droplets reflect one of the many aspects of deranged MAM function found in AD.

CUMC researchers have found evidence that Alzheimer’s disease (AD) may be caused by a massive increase in the physical and biochemical communication between two cell components, the endoplasmic reticulum (ER) and the mitochondrion. The finding has potential implications for the diagnosis and treatment of the disease.

The ER is a lacy network that distributes proteins within the cell. Mitochondria are the “power plants” of the cell, providing most of its energy. The outer membrane of the mitochondria associate with the ER in bridge-like structures called mitochondria-associated ER membranes (MAMs).

The MAMs regulate cholesterol, lipid, and calcium metabolism and transport—all of which are disturbed in AD. The MAM also contains a lipid metabolism enzyme required to produce amyloid—a major component of the plaques that accumulate in the brains of patients with AD.

Eric Schon, PhD, the Lewis P. Rowland Professor of Neurology (in Genetics and Development); Estela Area-Gomez, associate research scientist in the Department of Neurology; and their colleagues found that ER-mitochrondria communication at the MAM is greatly increased in brain cells of patients with the sporadic form of AD (99 percent of patients), as well as in those with the rare hereditary form of AD.

“Upregulated function of mitochondria-associated ER membranes in Alzheimer disease” was published on August 14, 2012 in the EMBO Journal.

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