Alzheimer Disease

  • Estela Area-Gomez
  • Eric A. Schon
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 997)


The most widely accepted hypothesis to explain the pathogenesis of Alzheimer disease (AD) is the amyloid cascade, in which the accumulation of extraneuritic plaques and intracellular tangles plays a key role in driving the course and progression of the disease. However, there are other biochemical and morphological features of AD, including altered calcium, phospholipid, and cholesterol metabolism and altered mitochondrial dynamics and function that often appear early in the course of the disease, prior to plaque and tangle accumulation. Interestingly, these other functions are associated with a subdomain of the endoplasmic reticulum (ER) called mitochondria-associated ER membranes (MAM). MAM, which is an intracellular lipid raft-like domain, is closely apposed to mitochondria, both physically and biochemically. These MAM-localized functions are, in fact, increased significantly in various cellular and animal models of AD and in cells from AD patients, which could help explain the biochemical and morphological alterations seen in the disease. Based on these and other observations, a strong argument can be made that increased ER-mitochondria connectivity and increased MAM function are fundamental to AD pathogenesis.


ApoE Cholesterol Cholesteryl esters Endoplasmic reticulum Lipid rafts MAM Membranes Mitochondria Mitochondria-associated ER membranes Neurodegeneration Phospholipids 



This work was supported by the US Department of Defense (W911F-15-1-0169), the Ellison Medical Foundation, and the J. Willard and Alice S. Marriott Foundation (to EAS) and by the US National Institutes of Health (K01-AG045335 to E.A.-G.).


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© Springer Nature Singapore Pte Ltd. 2017

Authors and Affiliations

  1. 1.Department of NeurologyColumbia University Medical CenterNew YorkUSA
  2. 2.Department of Genetics and DevelopmentColumbia University Medical CenterNew YorkUSA

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