Alzheimer’s disease (AD) and Dementia with Lewy bodies (DLB) are the two most common causes of dementia. In order to find effective treatments, it is critical that we understand the exact causes. Accumulation of Aβ and tau proteins in the brain occurs early in people with AD. In DLB, a protein called alpha-synuclein accumulates early inside neurons. We know that synapses, the most critical structures for communication between neurons, are lost very early in these diseases. However, the precise mechanism by which these proteins damage synapses is poorly understood due to the lack of adequate techniques. Here, we will apply the most advanced tools available to investigate the presence of abnormal proteins at synapses in a unique set of human brain samples. We will also investigate the effects of toxic proteins on synapse composition. This information will be invaluable for the development of more specific treatments for the two most common causes of dementia.