Neurochemical Characterization of PSA-NCAM+ Cells in the Human Brain and Phenotypic Quantification in Alzheimer’s Disease Entorhinal Cortex

• Published in: Neuroscience 2018-02, Vol.372, p.289-303
• Main Authors: Murray, Helen C., Swanson, Molly E.V., Dieriks, B. Victor, Turner, Clinton, Faull, Richard L.M., Curtis, Maurice A.
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer’s disease; Antigens, Nuclear - metabolism; Calbindin 2 - metabolism; Calbindins - metabolism; Cell Count; entorhinal cortex; Entorhinal Cortex - metabolism; Entorhinal Cortex - pathology; Female; Frontal Lobe - metabolism; Frontal Lobe - pathology; Hippocampus - metabolism; Hippocampus - pathology; Humans; interneuron; Interneurons - metabolism; Interneurons - pathology; Male; Middle Aged; Nerve Tissue Proteins - metabolism; neural cell adhesion molecule; Neural Cell Adhesion Molecule L1 - metabolism; Parvalbumins - metabolism; Phenotype; polysialic acid; Sialic Acids - metabolism; Temporal Lobe - metabolism; Temporal Lobe - pathology
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2017.12.019

•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. 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 mm2 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.