The pathological hallmarks of Alzheimer's disease (AD)--widespread synaptic and 
neuronal loss and the pathological accumulation of amyloid-beta peptide (Aβ) in 
senile plaques, as well as hyperphosphorylated tau in neurofibrillary 
tangles--have been known for many decades, but the links between AD pathology 
and dementia and effective therapeutic strategies remain elusive. Transgenic 
mice have been developed based on rare familial forms of AD and frontotemporal 
dementia, allowing investigators to test in detail the structural, functional, 
and behavioral consequences of AD-associated pathology. Here, we review work on 
transgenic AD models that investigate the degeneration of dendritic spine 
structure, synaptic function, and cognition. Together, these data support a 
model of AD pathogenesis in which soluble Aβ initiates synaptic dysfunction and 
loss, as well as pathological changes in tau, which contribute to both synaptic 
and neuronal loss. These changes in synapse structure and function as well as 
frank synapse and neuronal loss contribute to the neural system dysfunction 
which causes cognitive deficits. Understanding the underpinnings of dementia in 
AD will be essential to develop and evaluate therapeutic approaches for this 
widespread and devastating disease.