Your search for: 'author:("Algarzae, Norah K.")' has returned 2 results. (0.01s) Save search

Authors: Lonskaya, Irina | Shekoyan, Ashot R. | Hebron, Michaeline L. | Desforges, Nicole | Algarzae, Norah K. | Moussa, Charbel E.-H.

Article Type: Research Article

Abstract: Alzheimer's disease (AD) is an aging disorder characterized by amyloid-β (Aβ) accumulation in extracellular plaques and formation of intracellular tangles containing hyperphosphorylated tau (p-Tau). Autophagic defects, leading to accumulation of autophagosomes, are recognized in AD. Parkin is an E3 ubiquitin ligase involved in degradation of proteins via autophagy and the proteasome. We investigated the role of parkin in postmortem brain tissues from 21 AD patients and 15 control subjects. We detected decreased parkin solubility in AD cortex and parkin co-localization with intraneuronal Aβ1-42 in the hippocampus and cortex of AD patients. Parkin accumulation with intraneuronal Aβ and p-Tau was detected …in autophagosomes in AD brains. To determine the role of parkin in Aβ clearance, we generated gene transfer animals expressing lentiviral Aβ1-42 with and without parkin and examined autophagic mechanisms. Lentiviral expression of Aβ1-42 led to p-Tau accumulation and induced autophagic defects, leading to accumulation of autophagic vacuoles. However, co-expression of wild type parkin facilitated autophagic clearance and promoted deposition of Aβ1-42 and p-Tau into the lysosome. Taken together, these data suggest that Aβ1-42 alters normal autophagy and parkin enhances autophagic clearance. In conclusion, decreased parkin solubility may lead to co-localization with intraneuronal Aβ1-42 and compromise the cell autophagic clearance ability. Parkin may clear autophagic defects via autophagosome degradation. Show more

Keywords: amyloid-β, autophagy, parkin, tau phosphorylation

DOI: 10.3233/JAD-2012-121141

Citation: Journal of Alzheimer's Disease, vol. 33, no. 1, pp. 231-247, 2013

Authors: Rice, Ann C. | Keeney, Paula M. | Algarzae, Norah K. | Ladd, Amy C. | Thomas, Ravindar R. | Bennett Jr., James P.

Article Type: Research Article

Abstract: Alzheimer's disease (AD) is the major cause of adult-onset dementia and is characterized in its pre-diagnostic stage by reduced cerebral cortical glucose metabolism and in later stages by reduced cortical oxygen uptake, implying reduced mitochondrial respiration. Using quantitative PCR we determined the mitochondrial DNA (mtDNA) gene copy numbers from multiple groups of 15 or 20 pyramidal neurons, GFAP(+) astrocytes and dentate granule neurons isolated using laser capture microdissection, and the relative expression of mitochondrial biogenesis (mitobiogenesis) genes in hippocampi from 10 AD and 9 control (CTL) cases. AD pyramidal but not dentate granule neurons had significantly reduced mtDNA copy numbers …compared to CTL neurons. Pyramidal neuron mtDNA copy numbers in CTL, but not AD, positively correlated with cDNA levels of multiple mitobiogenesis genes. In CTL, but not in AD, hippocampal cDNA levels of PGC1α were positively correlated with multiple downstream mitobiogenesis factors. Mitochondrial DNA copy numbers in pyramidal neurons did not correlate with hippocampal Aβ1-42 levels. After 48 h exposure of H9 human neural stem cells to the neurotoxic fragment Aβ25-35 , mtDNA copy numbers were not significantly altered. In summary, AD postmortem hippocampal pyramidal neurons have reduced mtDNA copy numbers. Mitochondrial biogenesis pathway signaling relationships are disrupted in AD, but are mostly preserved in CTL. Our findings implicate complex alterations of mitochondria-host cell relationships in AD. Show more

Keywords: Laser capture microdissection, neural stem cells, PGC1 alpha, real-time PCR, TFAM

DOI: 10.3233/JAD-131715

Citation: Journal of Alzheimer's Disease, vol. 40, no. 2, pp. 319-330, 2014