Journal of Alzheimer's Disease - Volume 65, issue 4

Authors: Bloch, Konstantin | Gil-Ad, Irit | Vanichkin, Alexey | Hornfeld, Shay Henry | Taler, Michal | Dar, Shira | Azarov, Dmitry | Vardi, Pnina | Weizman, Abraham

Article Type: Research Article

Abstract: Background: Alzheimer’s disease (AD) is often associated with brain insulin resistance and peripheral metabolic dysfunctions. Recently, we developed a model of sporadic AD associated with obesity-related peripheral metabolic abnormalities in Lewis rats using intracerebroventricular administration of streptozotocin (icv-STZ). Objective: We aimed to assess the effect of intracranially grafted pancreatic islets on cognitive and peripheral metabolic dysfunctions in the icv-STZ Lewis rats. Methods: AD-like dementia associated with obesity was induced in inbred Lewis rats using a single icv-STZ. Two months after icv-STZ, syngeneic islets (100 islets per recipient) were implanted in the cranial subarachnoid …cavity of icv-STZ rats. Morris water maze and marble burying tests were used for studying cognitive and behavioral functions. Central and peripheral metabolic alterations were assessed by histological and biochemical assays. Results: The icv-STZ induced increases in food intake, body weight, and blood levels of insulin and leptin without alteration of glucose homeostasis. Grafted islets reduced body weight gain, food consumption, peripheral insulin resistance, and hyperleptinemia. Biochemical and histological analysis of the brain revealed viable grafted islets expressing insulin and glucagon. The grafted islets did not affect expression of brain insulin receptors and peripheral glucose homeostasis. Two months after islet transplantation, cognitive and behavioral functioning in transplanted rats were significantly better than the sham-operated icv-STZ rats. No significant differences in the locomotor activity between transplanted and non-transplanted icv-STZ rats were found. Conclusions: Intracranial islet transplantation attenuates cognitive decline and peripheral metabolic dysfunctions providing a novel therapeutic approach for sporadic AD associated with peripheral metabolic dysfunctions. Show more

Keywords: Alzheimer’s disease, animal models, dementia, obesity, pancreatic islet transplantation

DOI: 10.3233/JAD-180623

Citation: Journal of Alzheimer's Disease, vol. 65, no. 4, pp. 1445-1458, 2018

Authors: Hedderich, Dennis M. | Spiro, Judith E. | Goldhardt, Oliver | Kaesmacher, Johannes | Wiestler, Benedikt | Yakushev, Igor | Zimmer, Claus | Boeckh-Behrens, Tobias | Grimmer, Timo

Article Type: Research Article

Abstract: Background: Volumetric quantification of structural MRI has been shown to increase the diagnostic accuracy of patients with mild cognitive impairment (MCI); however, its implementation in clinical routine is usually technically difficult and time-consuming. Objective: The purpose of this study was to investigate whether volumetric information obtained from the free and easy-to-use online tool volBrain can improve correct identification of MCI patients with Alzheimer’s disease (AD) compared to visual reading. Methods: The study cohort consisted of 27 patients with MCI due to AD (AD positive) as determined by biomarker information and 26 cognitively normal controls (CN). Three …blinded readers, 2 radiologists and 1 clinical dementia expert, assessed the patients’ MRI regarding brain atrophy and probability of underlying AD two times, without and with supporting volumetric information from volBrain. To assess diagnostic accuracy of volBrain measures alone, a simple sum score based on basic volumetric measures was developed and tested. Results: Correct patient classification by readers 1, 2, and 3 without a volumetric report was 73.6%, 77.4%, and 83.0%. With a volumetric report, correct classification increased for the radiological readers to 77.4% and 81.1%, respectively and decreased to 77.4% for reader 3. Usage of the volumetric report alone yielded the highest diagnostic accuracy of 84.9%. Diagnostic confidence increased significantly for radiological readers. Conclusion: Volumetric information from volBrain increases the radiologist’s diagnostic performance and confidence in identifying MCI patients with AD. We propose that such tools may be implemented in the routine diagnostic work-up of patients with suspected AD. Show more

Keywords: Alzheimer’s disease, magnetic resonance imaging, mild cognitive impairment, neurodegenerative disease

DOI: 10.3233/JAD-180532

Citation: Journal of Alzheimer's Disease, vol. 65, no. 4, pp. 1459-1467, 2018

Authors: Garzón, Fernando | Coimbra, Débora | Parcerisas, Antoni | Rodriguez, Yamila | García, Julio Cesar | Soriano, Eduardo | Rama, Ramón

Article Type: Research Article

Abstract: Many experimental studies show that erythropoietin (EPO) has a neuroprotective action in the brain. EPO in acute and chronic neurological disorders, particularly in stroke, traumatic brain injury, Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis, has neuroprotective effects. We previously reported the neuroprotective effect of NeuroEPO, a low sialic form of EPO, against oxidative stress induced by glutamate excitotoxicity. In this paper, we analyze the effect of NeuroEPO against apoptosis induced by glutamate excitotoxicity in primary neuronal cultures obtained from the forebrains of Wistar rat embryos after 17 days of gestation. Excitotoxicity was induced after nine days of in vitro …culture by treatment with a culture medium containing 100μ M glutamate for 15 min. To withdraw glutamate, a new medium containing 100 ng NeuroEPO/mL was added. Apoptosis was analyzed after 24 h. Images obtained by phase contrast microscopy show that neurons treated with glutamate exhibit cell body shrinkage, loss of dendrites that do not make contact with neighboring cells, and that NeuroEPO was able to preserve the morphological characteristics of the control. Immunocytochemistry images show that the culture is essentially pure in neurons; that glutamate causes cell mortality, and that this is partially avoided when the culture medium is supplemented with NeuroEPO. Activation of intrinsic apoptotic pathways was analyzed. The decreases in Bcl-2/Bax ratio, increase in the release of cytochrome c, and in the expression and activity of caspase-3 observed in cells treated with glutamate, were restored by NeuroEPO. The results from this study show that NeuroEPO protects cortical neurons from glutamate-induced apoptosis via upregulation of Bcl-2 and inhibit glutamate-induced activation of caspase-3. Show more

Keywords: Apoptosis, erythropoietin, excitotoxicity, neurodegenerative diseases, NeuroEPO, neuroprotection

DOI: 10.3233/JAD-180668

Citation: Journal of Alzheimer's Disease, vol. 65, no. 4, pp. 1469-1483, 2018