Synaptic loss and dysfunction may be considered to take place in three ways:
1. Synapses are lost by the death of the neurons making those synapses. This fits into the pathogenic chain through neuron death.
2. Still living neurons lose synapses. This fits into the pathogenic chain through a number of potential mechanisms, largely involving tau and the cytoskeleton.
3. Synapses made by still living neurons and that are morphologically present can become dysfunctional. Understanding of the relation of this dysfunction to flavors of Aβ is proceeding nicely, largely through work from several laboratories.
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