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Physical basis of cognitive alterations in alzheimer's disease: Synapse loss is the major correlate of cognitive impairment
Dr. Robert D. Terry MD,
Eliezer Masliah MD,
David P. Salmon PhD,
Nelson Butters PhD,
Richard DeTeresa BS,
Robert Hill PhD,
Lawrence A. Hansen MD,
Robert Katzman MD,
Corresponding Author
Dr. Robert D. Terry MD
Department of Neurosciences, University of California—San Diego, La Jolla, CA
Department of Neurosciences M-024, University of California-San Diego, La Jolla, CA 92093-0624Search for more papers by this authorEliezer Masliah MD
Department of Neurosciences, University of California—San Diego, La Jolla, CA
Search for more papers by this authorDavid P. Salmon PhD
Department of Neurosciences, University of California—San Diego, La Jolla, CA
Search for more papers by this authorNelson Butters PhD
Department of Psychiatry, University of California—San Diego, La Jolla, CA
Search for more papers by this authorRichard DeTeresa BS
Department of Neurosciences, University of California—San Diego, La Jolla, CA
Search for more papers by this authorRobert Hill PhD
Department of Neurosciences, University of California—San Diego, La Jolla, CA
Search for more papers by this authorLawrence A. Hansen MD
Department of Neurosciences, University of California—San Diego, La Jolla, CA
Search for more papers by this authorRobert Katzman MD
Department of Neurosciences, University of California—San Diego, La Jolla, CA
Search for more papers by this authorDr. Robert D. Terry MD,
Eliezer Masliah MD,
David P. Salmon PhD,
Nelson Butters PhD,
Richard DeTeresa BS,
Robert Hill PhD,
Lawrence A. Hansen MD,
Robert Katzman MD,
Corresponding Author
Dr. Robert D. Terry MD
Department of Neurosciences, University of California—San Diego, La Jolla, CA
Department of Neurosciences M-024, University of California-San Diego, La Jolla, CA 92093-0624Search for more papers by this authorEliezer Masliah MD
Department of Neurosciences, University of California—San Diego, La Jolla, CA
Search for more papers by this authorDavid P. Salmon PhD
Department of Neurosciences, University of California—San Diego, La Jolla, CA
Search for more papers by this authorNelson Butters PhD
Department of Psychiatry, University of California—San Diego, La Jolla, CA
Search for more papers by this authorRichard DeTeresa BS
Department of Neurosciences, University of California—San Diego, La Jolla, CA
Search for more papers by this authorRobert Hill PhD
Department of Neurosciences, University of California—San Diego, La Jolla, CA
Search for more papers by this authorLawrence A. Hansen MD
Department of Neurosciences, University of California—San Diego, La Jolla, CA
Search for more papers by this authorRobert Katzman MD
Department of Neurosciences, University of California—San Diego, La Jolla, CA
Search for more papers by this authorAbstract
We present here both linear regressions and multivariate analyses correlating three global neuropsychological tests with a number of structural and neurochemical measurements performed on a prospective series of 15 patients with Alzheimer's disease and 9 neuropathologically normal subjects. The statistical data show only weak correlations between psychometric indices and plaques and tangles, but the density of neocortical synapses measured by a new immunocytochemical/densitometric technique reveals very powerful correlations with all three psychological assays. Multivariate analysis by stepwise regression produced a model including midfrontal and inferior parietal synapse density, plus inferior parietal plaque counts with a correlation coefficient of 0.96 for Mattis's Dementia Rating Scale. Plaque density contributed only 26% of that strength.
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