Affiliations: [a] Center for Psychiatric Neuroscience, CHUV, Lausanne, Switzerland | [b] Service of Old Age Psychiatry, Department of Psychiatry, CHUV, Lausanne, Switzerland | [c] Department of Psychiatry, Geneva University, HUG, Geneva, Switzerland | [d] Department of Cell Biology and Morphology, Lausanne University, Lausanne, Switzerland | [e] Department of Physiology, Lausanne University, Lausanne, Switzerland
Correspondence:
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Corresponding author: Dr. Geneviève Leuba, Center for Psychiatric Neuroscience, Department of Psychiatry, CHUV, CH-1008 Lausanne, Switzerland. Tel.: +4121 6436320; Fax: +4121 6436238; E-mail: Genevieve.Leuba@chuv.ch.
Abstract: We investigated how synaptic plasticity is related to the neurodegeneration process in the human dorsolateral prefrontal cortex. Pre- and postsynaptic proteins of Brodmann's area 9 from patients with Alzheimer's disease (AD) and age-matched controls were quantified by immunohistochemical methods and Western blots. The main finding was a significant increase in the expression of postsynaptic density protein PSD-95 in AD brains, revealed on both sections and immunoblots, while the expression of spinophilin, associated to spines, remained quantitatively unchanged despite qualitative changes with age and disease. Presynaptic protein α-synuclein indicated an increased immunohistochemical level, while synaptophysin remained unchanged. MAP2, a somatodendritic microtubule protein, as well as AD markers such as amyloid-β protein and phosphorylated protein tau showed an increased expression on immunosections in AD. Altogether these changes suggest neuritic and synaptic reorganization in the process of AD. In particular, the significant increase in PSD-95 expression suggests a change in NMDA receptors trafficking and may represent a novel marker of functional significance for the disease.
