Neurochemical Characterization of PSA-NCAM+ Cells in the Human Brain and Phenotypic Quantification in Alzheimer's Disease Entorhinal Cortex. (21st February 2018)

• Record Type: Journal Article
• Authors: Murray, Helen C.; Swanson, Molly E.V.; Dieriks, B. Victor; Turner, Clinton; Faull, Richard L.M.; Curtis, Maurice A.
• Is Part Of: Neuroscience. Volume 372(2018)
• Page Start: 289
• Page End: 303
• Publication Date: 2018-02-21
• Subjects: AD Alzheimer's disease -- CA1 Cornu Ammonis area 1 -- CAMKII Ca2+/calmodulin-dependent protein kinase II -- DARPP-32 dopamine- and cAMP-regulated neuronal phosphoprotein -- GAD glutamate decarboxylase -- GFAP glial fibrillary acid protein -- Iba1 ionized calcium-binding adapter molecule 1 -- PBS phosphate-buffered saline -- PSA-NCAM polysialylated neural cell adhesion molecule; polysialic acid -- neural cell adhesion molecule -- interneuron -- Alzheimer's disease -- entorhinal cortex; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2017.12.019
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: PSA-NCAM is expressed by interneurons in the adult human brain. PSA-NCAM + cells are decreased in the Alzheimer's disease entorhinal cortex. PSA-NCAM + /NeuN + cells are decreased in the Alzheimer's disease entorhinal cortex. Loss of PSA-NCAM + cells is not due to a specific loss of PSA-NCAM + calbindin or calretinin interneurons. Abstract: Polysialylated neural cell adhesion molecule (PSA-NCAM) is widely expressed in the adult human brain and facilitates structural remodeling of cells through steric inhibition of intercellular NCAM adhesion. We previously showed that PSA-NCAM immunoreactivity is decreased in the entorhinal cortex in Alzheimer's disease (AD). Based on available evidence, we hypothesized that a loss of PSA-NCAM + interneurons may underlie this reduction. PSA-NCAM expression by interneurons has previously been described in the human medial prefrontal cortex. Here we used postmortem human brain tissue to provide further evidence of PSA-NCAM + interneurons throughout the human hippocampal formation and additional cortical regions. Furthermore, PSA-NCAM + cell populations were assessed in the entorhinal cortex of normal and AD cases using fluorescent double labeling and manual cell counting. We found a significant decrease in the number of PSA-NCAM + cells per mm 2 in layer II and V of the entorhinal cortex, supporting our previous description of reduced PSA-NCAM immunoreactivity. Additionally, we found a significant decrease in the proportion of PSA-NCAM + cells that co-labeled with NeuN and parvalbumin, but no change in the proportion that co-labeled with calbindin or calretinin. These results demonstrate that PSA-NCAM is expressed by a variety of interneuron populations throughout the brain. Furthermore, that loss of PSA-NCAM expression by NeuN + cells predominantly contributes to the reduced PSA-NCAM immunoreactivity in the AD entorhinal cortex.