01.09.2014, Impact of a multi-nutrient diet on cognition, brain metabolism, hemodynamics, and plasticity in apoE4 carrier and apoE knockout mice.

Brain Struct Funct. 2014 Sep;219(5):1841-68.

Jansen D, Zerbi V, Janssen CI, van Rooij D, Zinnhardt B, Dederen PJ, Wright AJ, Broersen LM, Lütjohann D, Heerschap A, Kiliaan AJ.

In the present study, we tested the effects of long-term consumption of a specific multi-nutrient diet in mice models for atherosclerosis and hypercholesterolemia. This specific multi-nutrient diet was developed to protect the membranes of neurons and stimulate formation of contacts (synapses) between neurons. The specific multi-nutrient diet decreased anxiety-related behavior and increased the concentration of omega-3 fatty acids in the brain. Furthermore, we found that mice fed with this multi-nutrient diet showed locally increased cerebral circulation. Together, these data suggest that a specific dietary intervention has beneficial effects on early cerebral pathological consequences of an impaired vascular system. 

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21.08.2014, 2003-2013: A Decade of Body Mass Index, Alzheimer's Disease, and Dementia

J Alzheimers Dis. 2014 Aug 21.

Emmerzaal TL, Kiliaan AJ, Gustafson DR.

Overweight and obesity may increase risk for Alzheimer’s Disease (AD) and other dementias occurring in later life or after age 65 years Body Mass Index (BMI) is a common measure of overweight and obesity. BMI influences risk for dementia. Since BMI changes with age over the life course (increasing with increasing age during adult years, and decreasing with increasing age as one gets older) different dementia risk associations are observed in adulthood versus later life.  In midlife (to age 60 years), higher BMI increases risk for dementia. In late-life, higher BMI is protective for dementia.

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19.07.2014, Involvement of the Apoer2 and Lrp1 receptors in mediating the pathological effects of ApoE4 in vivo

Curr Alzheimer Res. 2014; 11(6):549-57.

Moran Gilat-Frenkel, Anat Boehm-Cagan, Ori Liraz, Xunde Xian, Joachim Herz, and Daniel M. Michaelson

In this study we investigated the effect of apoE4, the main genetic risk factor for Alzheimer's disease, on the levels of two ApoE-receptors, Apoer2 and Lrp1 in different experimental paradigms. We showed that naïve apoE4 mice have decreased levels of the ApoE receptor, Apoer2, while activation of the amyloid cascade results in up-regulation of the ApoE receptor Lrp1. This study show that the levels of hippocampal ApoE receptors Lrp1 and Apoer2 in vivo are affected isoform specifically by ApoE4 and that the type of receptor affected is context dependent.

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23.06.2014, Simultaneous changes of spatial memory and spine density after intrahippocampal administration of fibrillar Aβ1-42 to the rat brain.

Biomed Res Int. 2014 June; 2014:345305.

Anne Rijpma, Diane Jansen, Ilse Arnoldussen, Tsong Fang, Maximilian Wiesmann, Maartje Mutsaers, Jos Dederen, Carola Janssen and Amanda Kiliaan

Alzheimer’s disease has been the most frequent neurodegenerative disease with loss of memory. There are different animal models simulating the pathophysiological processes of Alzheimer’s disease. We used a rat model and found that injecting the toxic β-amyloid into the hippocampus caused simultaneous decrease of spatial memory and the number of synapses.

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16.06.2014, PS dependent APP cleavage regulates glucosylceramide synthase and is affected in Alzheimer's disease.

Cell Physiol Biochem. 2014 June 16; 34(1):92-110.

Grimm MO, Hundsdörfer B, Grösgen S, Mett J, Zimmer VC, Stahlmann CP, Haupenthal VJ, Rothhaar TL, Lehmann J, Pätzold A, Zinser EG, Tanila H, Shen J, Müller U, Grimm HS, Hartmann T.

Gangliosides are major lipids in human brain. It is well known that gangliosides influence the processes leading to Alzheimer´s disease. In this publication we elucidate that the link between ganglioside synthesis and the proteins involved in Alzheimer´s disease are bidirectional. Our results reveal complex regulatory cycles which are affected in Alzheimer´s disease and which are potential therapeutical targets.

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