Presenilin-1 (PS-1) mutations are associated with familial Alzheimer's disease (AD). Although beta-amyloid (Abeta) plaques in brain tissue are characteristic of AD patients, space occupying "cotton-wool" plaques (CWPs) lacking dense Abeta cores have also been described in patients with mutations in exon 9 of the PS-1 gene. The composition of CWPs has not been fully described. To better elucidate the composition of these space-occupying plaques, we used immunohistochemistry with antibodies to the synaptic proteins synapsin-1 and synaptophysin, as well as antibodies to tau, Abeta(-42), Abeta(-40), ubiquitin, neurofilament, and glial fibrillary acidic protein. Confocal laser scanning microscopy (CLSM) was utilized to further characterize these plaques. CWPs showed increased synapsin-1 and synaptophysin immunoreactivity relative to the background gray matter. Synaptic protein-containing CWPs occurred in all affected MTL regions, including the granule cell layer of the dentate gyrus, where synaptic terminals are usually sparse. These data suggest that in C410Y PS-1 AD patients, CWPs may constitute a major component of synaptic terminal-specific proteins, and that the C410Y PS-1 mutation may influence either synaptic structure or synaptic protein expression.