Characterization of a Drosophila Alzheimer's Disease Model: Pharmacological Rescue of Cognitive Defects

Transgenic models of Alzheimer's disease (AD) have made significant contributions to our understanding of AD pathogenesis, and are useful tools in the development of potential therapeutics. The fruit fly, Drosophila melanogaster, provides a genetically tractable, powerful system to study the biochemical, genetic, environmental, and behavioral aspects of complex human diseases, including AD. In an effort to model AD, we over-expressed human APP and BACE genes in the Drosophila central nervous system. Biochemical, neuroanatomical, and behavioral analyses indicate that these flies exhibit aspects of clinical AD neuropathology and symptomology. These include the generation of Aβ40 and Aβ42, the presence of amyloid aggregates, dramatic neuroanatomical changes, defects in motor reflex behavior, and defects in memory. In addition, these flies exhibit external morphological abnormalities. Treatment with a γ-secretase inhibitor suppressed these phenotypes. Further, all of these phenotypes are present within the first few days of adult fly life. Taken together these data demonstrate that this transgenic AD model can serve as a powerful tool for the identification of AD therapeutic interventions

Understanding the association between fatigue and neurocognitive functioning in patients with glioma: A cross-sectional multinational study

Abstract: Background: Fatigue and neurocognitive impairment are highly prevalent in patients with glioma, significantly impacting health-related quality of life. Despite the presumed association between these two factors, evidence remains sparse. Therefore, we aimed to investigate this relationship using multinational data. Methods: We analyzed data on self-reported fatigue and neurocognitive outcomes from postoperative patients with glioma from the University of California San Francisco (n = 100, UCSF) and Amsterdam University Medical Center (n = 127, Amsterdam UMC). We used multiple linear regression models to assess associations between fatigue and seven (sub)domains of neurocognitive functioning and latent profile analysis to identify distinct patterns of fatigue and neurocognitive functioning. Results: UCSF patients were older (median age 49 vs. 43 years, P = .002), had a higher proportion of grade 4 tumors (32% vs. 18%, P = .03), and had more neurocognitive deficits (P = .01). While the number of clinically fatigued patients was similar between sites (64% vs. 58%, P = .12), fatigue and the number of impaired neurocognitive domains were not correlated (P = .16–.72). At UCSF, neurocognitive domains were not related to fatigue, and at Amsterdam UMC attention and semantic fluency explained only 4–7% of variance in fatigue. Across institutions, we identified four distinct patterns of neurocognitive functioning, which were not consistently associated with fatigue. Conclusions: Although individual patients might experience both fatigue and neurocognitive impairment, the relationship between the two is weak. Consequently, both fatigue and neurocognitive functioning should be independently assessed and treated with targeted therapies

Sapientia, 2001, Vol. LVI, nº 209 (número completo)

Contenido: Lo connatural y el conocimiento por connaturalizad: Santo Tomás de Aquino / Ciro E. Schmidt Andrade – Santo Tomás de Aquino: la exégesis de la metafísica y la refutación del nominalismo / Mario Enrique Sacchi – Hacia un realismo hermenéutico sobre la base de Santo Tomás de Aquino-Husserl (1ª parte) / Gabriel J. Zanotti -- ¿La “cumbre” de la metafísica del idealismo alemán? / Martín Zubiría – Esencia y destino de la modernidad en Hegel / Francisco Leocata – El inconsciente espiritual y la supraconciencia del espíritu según Jacques Maritain / Martín Federico Echavarría – La Escuela de Frankfurt: reflexiones sobre el mal en la historia / Marisa Mosto – Nihilismo y tecnología: Hans Jonas y la filosofía de la historia / Amán Rosales Rodríguez – Las concepciones del mundo: reflexiones histórico-críticas acerca de un concepto ambiguo / Roberto J. Brie – Inferencia y conocimiento previo de lógica / Marisa Villalba de Tablón – El habitus principiorum y la luz intelectual / Lorenzo Vicente Burgoa – La necesidad de revalorizar la razón humana / María Celestina Donadío Maggi de Gandolfi – Democracia antigua y democracia liberal contemporánea / Jorge Martínez Barrera – Notas y comentarios – Bibliografí