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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01.03.2014, Sex Differences in Presynaptic Density and Neurogenesis in Middle-Aged ApoE4 and ApoE Knockout Mice

Journal of Neurodegenerative Diseases, Volume2013, Article ID 531326, 9 pages

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

Atherosclerosis and apolipoprotein E ε4 (APOE4) genotype are risk factors for Alzheimer’s disease (AD) and cardiovascular disease (CVD). Sex differences exist in prevalence and manifestation of both diseases. We investigated sex differences respective to aging, focusing on cognitive parameters in apoE4 and apoE knockout (ko) mouse models of AD and CVD. To our knowledge, no other studies investigating presynaptic density in aging female apoE4 or apoE ko mice are available. Sex-specific differences between APOE genotypes could account for some sex differences in AD and CVD.s

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01.03.2014, Body mass index, cognition, disability, APOE genotype and mortality: the "TREVISO LONGEVA (TRELONG)" Study.

Am J Geriatr Psychiatry. 2012 Jul;20(7):594-602

Gustafson D, Ongaro F, Meggiolaro S, Antuono P, Forloni GL, Albani D, Gajo GB, De Angeli S, Zanardo A Siculi M, Siculi G, Muffato G, Gava N, Regini C, Gallucci M.

Dynamic, interrelated late-life parameters, such as body mass index (BMI), cognition, and physical functioning on mortality in the elderly are unclear, as is the influence of APOE genotype. We explored these measures in relation to 7-year mortality in long-lived Italian elderly, comprising a representative, age-stratified, population sample from Treviso, Italy, the Treviso Longeva (TRELONG) Study. Three hundred eleven men and 357 women, aged 70 years and older (mean age 84 ± 8 years) were followed for seven-year mortality, which was evaluated in association with BMI, Mini-Mental State Examination (MMSE) score, Activities of Daily Living (ADL), APOE genotype, and a variety of clinical and survey data.
In separate age- and sex-adjusted analyses, BMI <18.5 kg/m(2), MMSE ≤24, and ADL <6, were associated with greater 7-year mortality among adults aged 70 years and older. In a multivariate model including all factors, MMSE ≤24, and ADL <6 were associated with greater mortality; BMI ≥30 kg/m(2) was protective. There were no interactions between BMI, MMSE, or ADL. When excluding those dying within 3 years of baseline, only an MMSE ≤24 was related to mortality. Higher MMSE score, higher ADL score, and higher BMI, independent of age, sex, and other factors, are markers for longer life among northern Italian adults aged 70 years or older. Global cognition, BMI, and physical functioning, assessed by short, simple tests are profound indicators of death within less than a decade.

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01.02.2014, Special lipid-based diets alleviate cognitive deficits in the APPswe/PS1dE9 transgenic mouse model of Alzheimer's disease independent of brain amyloid deposition

Journal of Nutritional Biochemistry. 2014 Feb; 25:157–169

Hennariikka Koivisto, Marcus O. Grimm, Tatjana L. Rothhaar, Róbert Berkecz, Dieter Lütjohann, Rajsa Giniatullina, Mari Takalo, Pasi O. Miettinen, Hanna-Maija Lahtinen, Rashid Giniatullin, Botond Penke, Tamás Janáky, Laus M. Broersen, Tobias Hartmann, Heikki Tanila

The omega-3 fatty acid docosahexaenoic acid (DHA) has been associated with decreased risk in Alzheimer disease in several epidemiological studies. This large preclinical study in Alzheimer model mice assessed the possibility to boost the DHA effect with additional nutrients. One combination of nutrients was particular effective in reversing the memory impairment, while another combination significantly lowered the brain levels of amyloid-beta peptide that is thought to be the main culprit of the disease. The study demontrates the treatment potential of lipid-based diets in an early stage of the disease.

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01.02.2014, Unfolded protein response signaling by transcription factor XBP-1 regulates ADAM10 and is affected in Alzheimer's disease.

FASEB J., 2014 Feb;28(2):978-97.

Reinhardt S, Schuck F, Grösgen S, Riemenschneider M, Hartmann T, Postina R, Grimm M, Endres K.

In Alzheimer´s disease the APP processing is shifted from the protective non-amyloidogenic pathway to the amyloidogenic pathway leading to Ab production, one of the major components of senile plaques. Therefore one aim is to identify pathways leading to an increased protective non-amyloidogenic pathway. In this study we have identified the protein XBP1 in regulating the non-amyloidogenic pathways and identified the underlying mechanisms. XBP1 is a protein being involved in the stress response of cells, especially in the unfolded protein response. Further experiments revealed these regulating mechanisms and the link to the non-amyloidogenic pathway are disturbed in case of Alzheimer´s disease.

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