This brief paper reviews the work on dementia by the Neuropathology group at the Einstein College of Medicine and later at the University of California, San Diego, from the time of our first approaches to Alzheimer Disease in 1959. The electron microscope studies concerned the tangle (got it wrong) and then the plaque (got it right). Lysosomes and active microglia were noted in the plaques. Axoplasmic transport was suggested to be abnormal. We studied the plaques in old dogs and old monkeys, and then went on to use image analysis to count neurons in the neocortex of Alzheimer cases and in examples of normal aging. Later in San Diego we quantified presynaptic boutons and recognized their loss as the major direct cause of dementia. Many collaborators including Henry Wisniewski participated in these early attempts to understand the disease.
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