21.05.2014, Reversal of apoE4-Driven Brain Pathology and Behavioral Deficits by Bexarotene

The Journal of Neuroscience. 2014 May 21; 34(21):7293-7301.

Anat Boehm-Cagan and Daniel M. Michaelson

In the present study, we investigated the extent to which a pharmacological approach can correct the lipidation deficiency of apoE4, the main genetic risk factor for Alzheimer's disease, and correct the apoE4-driven pathologies. We found that the RXR agonist bexarotene can reverse the lipidation deficiency of apoE4 and the cognitive impairments and the associated neuronal deficits of apoE4 mice.

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17.05.2014, ApoE4 induces Aβ42, tau, and neuronal pathology in the hippocampus of young targeted replacement apoE4 mice.

Molecular Neurodegeneration. 2013 May 17; 8:16.

Liraz O, Boehm-Cagan A, Michaelson DM.

ApoE4 is the major genetic risk factor for Alzheimer's disease. Studies have shown that the pathological effects of apoE4 start decades before the onset of the disease. We developed a model to study the early onset pathological effects of apoE4. This model revealed that apoE4 induces cognitive deficits associated with neuronal and synaptic pathology.

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13.05.2014, Changes in Membrane Cholesterol Differentially Influence Preferential and Non-preferential Signaling of the M1 and M3 Muscarinic Acetylcholine Receptors.

Neurochem Res. 2014 May 13. [Epub ahead of print]

Pavel Michal, Esam E. El-Fakahany, Vladimir Dolezal

The M1 muscarinic receptor is a major cerebral muscarinic receptor subtype that is essential for cognitive functions. In addition, activation of the M1, and also the M3, subtype of muscarinic receptor increases non-amyloidogenic processing of amyloid precursor protein.  Any malfunction of the M1 receptor-mediated signaling may thus adversely impact not only mental performance but also amyloid precursor protein processing and increase amyloid-β generation. Here we demonstrate that particularly the decrease in membrane cholesterol impairs the M1 receptor-mediated signal transduction across plasma membrane and may thus contribute to the progression of beta-amyloid accumulation and cognitive decline in Alzheimer´s disease.

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11.04.2014, The relationships of phytosterols and oxyphytosterols in plasma and aortic valve cusps in patients with severe aortic stenosis

Biochem Biophys Res Commun. 2014 Apr 11; 446(3):805-10.

Hans-Frieder Schött, Alexandra Luister, Constanze Husche, Hans-Joachim Schäfers, Michael Böhm, Jogchum Plat, Dieter Lütjohann, Ulrich Laufs, Oliver Weingärtner

Plant sterols (PS) and oxyphytosterols (OPS) were determined in plasma and aortic valve cusp that were pre-analytically differenciated in valve tissue and atherosclerotic plaque. PS correlate strongly in and between plasma and valve cusps tissue. OPS correlate strongly in valve cusps tissue. PS and POP correlate strongly in valve cusps tissue.

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01.03.2014, Multinutrient diets improve cerebral perfusion and neuroprotection in a murine model of Alzheimer's disease.

Neurobiology of Aging 2014 Mar;35(3):600-13.

Valerio Zerbi, Diane Jansen, Maximilian Wiesmann, Tsong Fang, Laus Broersen, Andor Veltien, Arend Heerschap, Amanda Kiliaan

Nutritional intervention may retard the development of Alzheimer's disease (AD).
In this study we tested the effects of 2 multi-nutrient diets in an AD mouse model. The diets were developed to enhance contacts/connections  between nerve cells and improve the vascular health. We measured the cerebral blood flow (CBF) and the connections within the brain with imaging methods. Alzheimer mice have a decreased CBF and loss of brain connections like in patients with AD. Both multinutrient diets were able to increase CBF and connections in the mice brains. We suggest that a specific diet intervention has the potential to slow AD progression, by simultaneously improving cerebrovascular health and enhancing neuroprotective mechanisms.

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