Affiliations: Department 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 | Department of Neurosciences, University of California,
San Diego, CA, USA | Banner Alzheimer's Institute, Phoenix, AZ, USA
Note: [] Corresponding author: Adam S. Fleisher, MD, Banner Alzheimer's
Institute, 901 E Willetta Street, Phoenix, AZ 85383, USA. Tel.: +1 602 239
6979; Fax: +1 602 239 6499; E-mail: adam. fleisher@bannerhealth.com
Abstract: 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.
