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Behavioural Neurology
Volume 21 (2009), Issue 1-2, Pages 93-100

Pinpointing Synaptic Loss Caused by Alzheimer’s Disease with fMRI

Adam M. Brickman,1 Scott A. Small,1 and Adam Fleisher2,3

1Department of Neurology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA
2Department of Neurosciences, University of California, San Diego, CA, USA
3Banner Alzheimer's Institute, Phoenix, AZ, USA

Received 16 October 2009; Accepted 16 October 2009

Copyright © 2009 Hindawi Publishing Corporation and the authors. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


During its earliest stage, before cell loss and independent of amyloid plaques and neurofibrillary tangles, Alzheimer's disease (AD) causes synaptic loss affecting the basal functional properties of neurons. In principle, synaptic loss can be detected by measuring AD-induced changes in basal function, or by measuring stimulus-evoked responses on top of basal changes. Functional magnetic resonance imaging (fMRI) is sensitive to both basal changes and evoked-responses, and there are therefore two experimental approaches in which fMRI can be used to pinpoint synaptic loss in AD. In this review, we will compare and contrast both approaches for pinpointing when and where synaptic loss in AD begins and for monitoring therapeutic efficacy.