- Email: [email protected]
HOW TO CHOOSE EXPERIMENTAL SYSTEMS TO EVALUATE PHARMACEUTICAL PREPARATIONS TO TREAT ALZHEIMER'S DISEASE
P630
Poster Presentations: Monday, July 25, 2016
association was weaker among MA (r ¼ 0.14, p < 0.001). AREG mediated their association only in NHW. Conclusions: APOE’s association with dementia severity is significant in both MA and NHW, but weaker in MA. AREG mediates APOE’s association with dementia severity, but only in NHW. This analysis contributes to the growing literature of ethnicity-specific serum protein effects on cognition.
P2-058
HOW TO CHOOSE EXPERIMENTAL SYSTEMS TO EVALUATE PHARMACEUTICAL PREPARATIONS TO TREAT ALZHEIMER’S DISEASE
Yenela Garcıa1, Claudio Rodrıguez–Martınez Sr.1, Active biomolecules in neurologycal disorders, 1National Center of Bioproducts, Bejucal, Cuba. Contact e-mail: [email protected] Background: Alzheimer disease (AD) is characterized by accu-
mulation of amyloid-b plaques from the amyloid precursor protein, neurofibrillary tangles, widespread synaptic loss, inflammation, oxidative damage and neuronal death. Animal models have become an indispensable tool, both to increase the knowledge about the pathology of the disease, as well as, for the discovery of novel pharmaceutical preparations for the treatment of AD. However, there are a lot of examples of pharmaceutical preparations that have been developed for the treatment of AD and the results obtained in preclinical studies, have not been reproduced in the clinical studies. Among the causes of low clinical efficacy of these pharmaceutical preparations, it is the choosing of the suitable animal model during the preclinical phase of research. The objective of this work it’s to propose a strategy to allow us to minimize such difficulty. Methods: We suggest starting with identification of the therapeutic “goal” of the preparation inside the physiology of the AD. Another phase should be to choose the specific groups of patients to evaluate the preparation, and finally to select the appropriate experimental models, or the combination of them. This last step should take into account a logical sequential order of complexity, from in vitro to in vivo experimental models. Results: As an example of application of the proposed strategy, this work includes the selection of animal models to evaluate natural products to revert the insulin resistance and the neuroinflammation. Conclusions: This strategy contributed to increase the quality of preclinical studies.
P2-059
INTRANEURONAL AMYLIN DEPOSITION, PEROXIDATIVE MEMBRANE INJURY AND INCREASED IL-1SS SYNTHESIS IN BRAINS OF ALZHEIMER’S DISEASE PATIENTS WITH TYPE-2 DIABETES AND DIABETIC HIP RATS
Florin Despa, Nirmal Verma, Han Ly, Miao Liu, Jing Chen, Haining Zhu, Louis Hersh, University of Kentucky, Lexington, KY, USA. Contact e-mail: [email protected] Background: Recent studies, including work from our laboratory,
suggest that type-2 diabetes is linked with Alzheimer’s disease (AD) by the interaction of amylin (also known as islet amyloid polypeptide) with ß amyloid pathology. Here, we sought to spectroscopically authenticate the presence of amylin in AD brains and identify specific amylin-mediated neurotoxic mechanisms. Methods: The presence of amylin in brain specimens from AD patients with type-2 diabetes (n¼4) was tested by liquid chromatography tandem mass spectrometry (LC-MS/MS). To decipher
Poster Presentations: Monday, July 25, 2016
association was weaker among MA (r ¼ 0.14, p < 0.001). AREG mediated their association only in NHW. Conclusions: APOE’s association with dementia severity is significant in both MA and NHW, but weaker in MA. AREG mediates APOE’s association with dementia severity, but only in NHW. This analysis contributes to the growing literature of ethnicity-specific serum protein effects on cognition.
P2-058
HOW TO CHOOSE EXPERIMENTAL SYSTEMS TO EVALUATE PHARMACEUTICAL PREPARATIONS TO TREAT ALZHEIMER’S DISEASE
Yenela Garcıa1, Claudio Rodrıguez–Martınez Sr.1, Active biomolecules in neurologycal disorders, 1National Center of Bioproducts, Bejucal, Cuba. Contact e-mail: [email protected] Background: Alzheimer disease (AD) is characterized by accu-
mulation of amyloid-b plaques from the amyloid precursor protein, neurofibrillary tangles, widespread synaptic loss, inflammation, oxidative damage and neuronal death. Animal models have become an indispensable tool, both to increase the knowledge about the pathology of the disease, as well as, for the discovery of novel pharmaceutical preparations for the treatment of AD. However, there are a lot of examples of pharmaceutical preparations that have been developed for the treatment of AD and the results obtained in preclinical studies, have not been reproduced in the clinical studies. Among the causes of low clinical efficacy of these pharmaceutical preparations, it is the choosing of the suitable animal model during the preclinical phase of research. The objective of this work it’s to propose a strategy to allow us to minimize such difficulty. Methods: We suggest starting with identification of the therapeutic “goal” of the preparation inside the physiology of the AD. Another phase should be to choose the specific groups of patients to evaluate the preparation, and finally to select the appropriate experimental models, or the combination of them. This last step should take into account a logical sequential order of complexity, from in vitro to in vivo experimental models. Results: As an example of application of the proposed strategy, this work includes the selection of animal models to evaluate natural products to revert the insulin resistance and the neuroinflammation. Conclusions: This strategy contributed to increase the quality of preclinical studies.
P2-059
INTRANEURONAL AMYLIN DEPOSITION, PEROXIDATIVE MEMBRANE INJURY AND INCREASED IL-1SS SYNTHESIS IN BRAINS OF ALZHEIMER’S DISEASE PATIENTS WITH TYPE-2 DIABETES AND DIABETIC HIP RATS
Florin Despa, Nirmal Verma, Han Ly, Miao Liu, Jing Chen, Haining Zhu, Louis Hersh, University of Kentucky, Lexington, KY, USA. Contact e-mail: [email protected] Background: Recent studies, including work from our laboratory,
suggest that type-2 diabetes is linked with Alzheimer’s disease (AD) by the interaction of amylin (also known as islet amyloid polypeptide) with ß amyloid pathology. Here, we sought to spectroscopically authenticate the presence of amylin in AD brains and identify specific amylin-mediated neurotoxic mechanisms. Methods: The presence of amylin in brain specimens from AD patients with type-2 diabetes (n¼4) was tested by liquid chromatography tandem mass spectrometry (LC-MS/MS). To decipher