Social and Behavioral Sciences Commons^™

Elevated Stearoyl-Coa Desaturase In Brains Of Patients With Alzheimer's Disease, Giuseppe Astarita, Kwang-Mook Jung, Vitaly Vasilevko, Nicholas V. Dipatrizio, Sarah K. Martin, David H. Cribbs, Elizabeth Head, Carl W. Cotman, Daniele Piomelli

Sanders-Brown Center on Aging Faculty Publications

The molecular bases of Alzheimer's disease (AD) remain unclear. We used a lipidomic approach to identify lipid abnormalities in the brains of subjects with AD (N = 37) compared to age-matched controls (N = 17). The analyses revealed statistically detectable elevations in levels of non-esterified monounsaturated fatty acids (MUFAs) and mead acid (20:3n-9) in mid-frontal cortex, temporal cortex and hippocampus of AD patients. Further studies showed that brain mRNAs encoding for isoforms of the rate-limiting enzyme in MUFAs biosynthesis, stearoyl-CoA desaturase (SCD-1, SCD-5a and SCD-5b), were elevated in subjects with AD. The monounsaturated/saturated fatty acid ratio ('desaturation index')--displayed a strong …

Activation Of Matrix Metalloproteinases Following Anti-Aβ Immunotherapy; Implications For Microhemorrhage Occurrence, Donna M. Wilcock, Dave Morgan, Marcia N. Gordon, Tiffany L. Taylor, Lisa A. Ridnour, David A. Wink, Carol A. Colton

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Anti-Aβ immunotherapy is a promising approach to the prevention and treatment of Alzheimer's disease (AD) currently in clinical trials. There is extensive evidence, both in mice and humans that a significant adverse event is the occurrence of microhemorrhages. Also, vasogenic edema was reported in phase 2 of a passive immunization clinical trial. In order to overcome these vascular adverse effects it is critical that we understand the mechanism(s) by which they occur.

METHODS: We have examined the matrix metalloproteinase (MMP) protein degradation system in two previously published anti-Aβ immunotherapy studies. The first was a passive immunization study in which …

Epigenetic Silencing Of Nucleolar Rrna Genes In Alzheimer's Disease, Maciej Pietrzak, Grzegorz Rempala, Peter T. Nelson, Jing-Juan Zheng, Michal Hetman

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Ribosomal deficits are documented in mild cognitive impairment (MCI), which often represents an early stage Alzheimer's disease (AD), as well as in advanced AD. The nucleolar rRNA genes (rDNA), transcription of which is critical for ribosomal biogenesis, are regulated by epigenetic silencing including promoter CpG methylation.

METHODOLOGY/PRINCIPAL FINDINGS: To assess whether CpG methylation of the rDNA promoter was dysregulated across the AD spectrum, we analyzed brain samples from 10 MCI-, 23 AD-, and, 24 age-matched control individuals using bisulfite mapping. The rDNA promoter became hypermethylated in cerebro-cortical samples from MCI and AD groups. In parietal cortex, the rDNA promoter …

Common And Distinct Mechanisms Of Cognitive Flexibility In Prefrontal Cortex, Chobok Kim, Nathan F. Johnson, Sara E. Cilles, Brian T. Gold

Neuroscience Faculty Publications

The human ability to flexibly alternate between tasks represents a central component of cognitive control. Neuroimaging studies have linked task switching with a diverse set of prefrontal cortex (PFC) regions, but the contributions of these regions to various forms of cognitive flexibility remain largely unknown. Here, subjects underwent functional brain imaging while they completed a paradigm that selectively induced stimulus, response, or cognitive set switches in the context of a single task decision performed on a common set of stimuli. Behavioral results indicated comparable reaction time costs associated with each switch type. Domain-general task-switching activation was observed in the inferior …

Cx3cl1 Reduces Neurotoxicity And Microglial Activation In A Rat Model Of Parkinson's Disease, Mibel M. Pabon, Adam D. Bachstetter, Charles E. Hudson, Carmelina Gemma, Paula C. Bickford

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Parkinson's disease is characterized by a progressive loss of dopaminergic neurons in the substantia nigra. The cause of the neurodegeneration is unknown. Neuroinflammation has been clearly shown in Parkinson's disease and may be involved in the progressive nature of the disease. Microglia are capable of producing neuronal damage through the production of bioactive molecules such as cytokines, as well as reactive oxygen species (ROS), and nitric oxide (NO). The inflammatory response in the brain is tightly regulated at multiple levels. One form of immune regulation occurs via neurons. Fractalkine (CX3CL1), produced by neurons, suppresses the activation of microglia. CX3CL1 …