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Presenilin-1 C410Y Alzheimer Disease Plaques Contain Synaptic Proteins

Drexel University College of Medicine, Philadelphia, Pennsylvania

Carol F. Lippa, MD

Drexel University College of Medicine, Philadelphia, Pennsylvania, clippa{at}drexelmed.edu

Thomas W. Smith, MD

University of Massachusetts Medical School, Worcester, Massachusetts

Hisatomo Kowa, PhD

University of Tokyo, Japan

Jianlin Wu, PhD

Drexel University College of Medicine, Philadelphia, Pennsylvania

Takeshi Iwatsubo, MD

University of Tokyo, Japan

Presenilin-1 (PS-1) mutations are associated with familial Alzheimer's disease (AD). Although beta-amyloid (Aß) plaques in brain tissue are characteristic of AD patients, space occupying "cotton-wool" plaques (CWPs) lacking dense Aß 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, Aß_-42, Aß_-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.

Key Words: Alzheimer's disease • beta-amyloid • presenilin-1 • regeneration • synapse • synaptophysin

American Journal of Alzheimer's Disease and Other Dementias®, Vol. 22, No. 2, 137-144 (2007)
DOI: 10.1177/1533317506298051


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