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Biochemical Characterization of Mouse Retina of an Alzheimer's Disease Model by Raman Spectroscopy

Stiebing, C. (author), Jahn, I.J. (author), Schmitt, M. (author), Keijzer, N. (author), Kleemann, R. (author), Kiliaan, A.J. (author), Drexler, W. (author), Leitgeb, R.A. (author), Popp, J. (author)

The presence of biomarkers characteristic for Alzheimer's disease in the retina is a controversial topic. Raman spectroscopy offers information on the biochemical composition of tissues. Thus, it could give valuable insight into the diagnostic value of retinal analysis. Within the present study, retinas of a double transgenic mouse model, that...

article 2020

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Low-grade inflammation, diet composition and health: Current research evidence and its translation

Minihane, A.M. (author), Vinoy, S. (author), Russell, W.R. (author), Baka, A. (author), Roche, H.M. (author), Tuohy, K.M. (author), Teeling, J.L. (author), Blaak, E.E. (author), Fenech, M. (author), Vauzour, D. (author), McArdle, H.J. (author), Kremer, B.H.A. (author), Sterkman, L. (author), Vafeiadou, K. (author), Benedetti, M.M. (author), Williams, C.M. (author), Calder, P.C. (author)

The importance of chronic low-grade inflammation in the pathology of numerous age-related chronic conditions is now clear. An unresolved inflammatory response is likely to be involved from the early stages of disease development. The present position paper is the most recent in a series produced by the International Life Sciences Institute's...

article 2015

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Supporting daily activities and indoor travel of persons with moderate Alzheimer's disease through standard technology resources

Lancioni, G.E. (author), Singh, N.N. (author), O'Reilly, M.F. (author), Sigafoos, J. (author), Renna, C. (author), Ventrella, M. (author), Pinto, K. (author), Minervini, M.G. (author), Oliva, D. (author), Groenewegen, J. (author)

These two studies were aimed at evaluating standard technology resources for supporting activity and travel among patients with moderate Alzheimer's disease. Specifically, Study I assessed a pictorial instruction program relying on the use of a portable computer and a commercially available and inexpensive video editing software for supporting...

article 2013

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Assessing the impact and social perception of self-regulated music stimulation with patients with Alzheimer's disease

Lancioni, G.E. (author), O'Reilly, M.F. (author), Singh, N.N. (author), Sigafoos, J. (author), Grumo, G. (author), Pinto, K. (author), Stasolla, F. (author), Signorino, M. (author), Groenewegen, J. (author)

We assessed the impact and social rating of an active and a passive music condition implemented with six patients with Alzheimer's disease. In the active condition, the patients used a simple hand response and a microswitch to self-regulate music stimulation inputs. In the passive condition, music stimulation was automatically presented...

article 2013

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Technology-based orientation programs to support indoor travel by persons with moderate Alzheimer's disease: Impact assessment and social validation

Lancioni, G.E. (author), Perilli, V. (author), O'Reilly, M.F. (author), Singh, N.N. (author), Sigafoos, J. (author), Bosco, A. (author), Caffo, A.O. (author), Picucci, L. (author), Cassano, G. (author), Groenewegen, J. (author)

The present study (a) extended the assessment of an orientation program involving auditory cues (i.e., verbal messages automatically presented from the destinations) with five patients with Alzheimer's disease, (b) compared the effects of this program with those of a program with light cues (i.e., a program in which strobe lights were used...

article 2013

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Bace1 activity in cerebrospinal fluid and its relation to markers of ad pathology

Mulder, S.D. (author), van der Flier, W.M. (author), Verheijen, J.H. (author), Mulder, C. (author), Scheltens, P. (author), Blankenstein, M.A. (author), Hack, C.E. (author), Veerhuis, R. (author), TNO Kwaliteit van Leven (author)

Several studies have shown that reduced amyloid-β 1-42 (Aβ {42}) and increased tau levels in cerebrospinal fluid (CSF) reflect increased Alzheimer's disease (AD) pathology in the brain. β-site APP cleaving enzyme (BACE1) is thought to be the major β-secretase involved in Aβ production in the brain, and therefore we investigated the relation...

article 2010

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Translational research in genomics of Alzheimer's disease: A review of current practice and future perspectives

Mihaescu, R. (author), Detmar, S.B. (author), Cornel, M.C. (author), van der Flier, W.M. (author), Heutink, P. (author), Hol, E.M. (author), Rikkert, M.G.M.O. (author), van Duijn, C.M. (author), Janssens, A.C.J.W. (author), TNO Kwaliteit van leven (author)

Alzheimer's disease (AD) is the most prevalent form of dementia and the number of cases is expected to increase exponentially worldwide. Three highly penetrant genes (AβPP, PSEN1, and PSEN2) explain only a small number of AD cases with a Mendelian transmission pattern. Many genes have been analyzed for association with non-Mendelian AD, but the...

article 2010

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Analytical strategies in lipidomics and applications in disease biomarker discovery

Hu, C. (author), van der Heijden, R. (author), Wang, M. (author), van der Greef, J. (author), Hankemeier, T. (author), Xu, G. (author), TNO Kwaliteit van Leven (author)

Lipidomics is a lipid-targeted metabolomics approach aiming at comprehensive analysis of lipids in biological systems. Recently, lipid profiling, or so-called lipidomics research, has captured increased attention due to the well-recognized roles of lipids in numerous human diseases to which lipid-associated disorders contribute, such as diabetes...

article 2009

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Stress proteins in CNS inflammation

van Noort, J.M. (author), TNO Kwaliteit van Leven (author)

Stress proteins or heat shock proteins (HSPs) are ubiquitous cellular components that have long been known to act as molecular chaperones. By assisting proper folding and transport of proteins, and by assisting in the degradation of aberrant proteins, they play key roles in cellular metabolism. The frequent accumulation of insoluble protein...

article 2008

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Human apolipoprotein C-I expression in mice impairs learning and memory functions

TNO Kwaliteit van Leven (author), Abildayeva, K. (author), Berbée, J.F.P. (author), Blokland, A. (author), Jansen, P.J. (author), Hoek, F.J. (author), Meijer, O. (author), Lütjohann, D. (author), Gautier, T. (author), Pillot, T. (author), Vente, J.de (author), Havekes, L.M. (author), Ramaekers, F.C.S. (author), Kuipers, F. (author), Rensen, P.C.N. (author), Mulder, M. (author)

The H2 allele of APOC1, giving rise to increased gene expression of apolipoprotein C-I (apoC-I), is in genetic disequilibrium with the APOE4 allele and may provide a major risk factor for Alzheimer's disease (AD). We found that apoC-I protein is present in astrocytes and endothelial cells within hippocampal regions in both human control and AD...

article 2008

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LDL receptor deficiency results in decreased cell proliferation and presynaptic bouton density in the murine hippocampus

Mulder, M. (author), Koopmans, G. (author), Wassink, G. (author), Mansouri, G.A. (author), Simard, M.-L. (author), Havekes, L.M. (author), Prickaerts, J. (author), Blokland, A. (author), TNO Kwaliteit van Leven (author)

An aberrant cholesterol metabolism in the brain may contribute to the pathogenesis of Alzheimer's disease (AD). The LDL receptor (LDLR) regulates plasma cholesterol levels and recently we and others obtained evidence that it is also involved in regulating brain cholesterol homeostasis. Moreover, we found that LDLR-deficient mice display impaired...

article 2007

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Detection of a soluble form of BACE-1 in human cerebrospinal fluid by a sensitive activity assay

TNO Kwaliteit van Leven (author), Verheijen, J.H. (author), Huisman, L.G.M. (author), van Lent, N. (author), Neumann, U. (author), Paganetti, P. (author), Erik Hack, C. (author), Bouwman, F. (author), Lindeman, J. (author), Bollen, E.L.E.M. (author), Hanemaaijer, R. (author)

Background: Formation of deposits of the insoluble amyloid β-peptide is believed to be causally related with neurodegeneration in Alzheimer disease (AD). The β-peptide originates from a larger amyloid precursor protein (APP) by the action of proteolytic enzymes. The first proteolytic event leading to amyloid formation is the cleavage of APP by...

article 2006

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Inhibition of microglial inflammation by the MLK inhibitor CEP-1347

TNO Preventie en Gezondheid (author), Lund, S. (author), Porzgen, P. (author), Mortensen, A.L. (author), Hasseldam, H. (author), Bozyczko-Coyne, D. (author), Morath, S. (author), Hartung, T. (author), Bianchi, M. (author), Ghezzi, P. (author), Bsibsi, M. (author), Dijkstra, S. (author), Leist, M. (author)

CEP-1347 is a potent inhibitor of the mixed lineage kinases (MLKs), a distinct family of mitogen-activated protein kinase kinase kinases (MAPKKK). It blocks the activation of the c-Jun/JNK apoptotic pathway in neurons exposed to various stressors and attenuates neurodegeneration in animal models of Parkinson's disease (PD). Microglial activation...

article 2005

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Low-density lipoprotein receptor-knockout mice display impaired spatial memory associated with a decreased synaptic density in the hippocampus

Mulder, M. (author), Jansen, P.J. (author), Janssen, B.J.A. (author), van de Berg, W.D.J. (author), van der Boom, H. (author), Havekes, L.M. (author), de Kloet, R.E. (author), Ramaekers, F.C.S. (author), Blokland, A. (author), TNO Preventie en Gezondheid (author)

The low-density lipoprotein receptor (LDLR) is the first described receptor for apolipoprotein E (apoE). We hypothesize that the absence of the LDLR, similar to the absence of apoE, results in impaired learning and memory processes. Six-month-old homozygous Ldlr-/- and wild-type littermates (Ldlr+/+), maintained on a standard lab chow diet, were...

article 2004

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Broad expression of Toll-like receptors in the human central nervous system

Bsibsi, M. (author), Ravid, R. (author), Gveric, D. (author), van Noort, J.M. (author)

The family of Toll-like receptors (TLRs) plays a key role in controlling innate immune responses to a wide variety of pathogen-associated molecules. In this study we investigated expression of TLRs in vitro by purified human microglia, astrocytes, and oligodendrocytes, and in vivo by immunohistochemical examination of brain and spinal cord...

article 2002

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Circadian and age-related modulation of thermoreception and temperature regulation: Mechanisms and functional implications

van Someren, E.J.W. (author), Raymann, R.J.E.M. (author), Scherder, E.J.A. (author), Daanen, H.A.M. (author), Swaab, D.F. (author), TNO Technische Menskunde (author)

At older ages, the circadian rhythm of body temperature shows a decreased amplitude, an advanced phase, and decreased stability. The present review evaluates to what extent these changes may result from age-related deficiencies at several levels of the thermoregulatory system, including thermoreception, thermogenesis and conservation, heat loss,...

article 2002

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Signalering van beginnende Alzheimer-dementie in de huisartspraktijk: Ontwikkeling en validering van de observatie lijst voor vroege symptomen van dementie (OLD) [Observation of early symptoms of Alzheimer dementia in general practice: Development and validation of the observation list for early signs of dementia (OLD)]

Hopman-Rock, M. (author), Tak, E.C.P.M. (author), Staats, P.G.M. (author), Jonker, C. (author), Wind, A.W. (author)

Aim of the study was the development and validation of a short observation list of possible early signs of dementia (OLD) for use in general practice. A stepwise development was carried out using reviews of publications and expert consensus. Experimental observations were carried out by 22 general practitioners in 19 Dutch practices. A field...

article 2001

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Development and validation of the observation list for early signs of dementia (OLD)

Hopman-Rock, M. (author), Tak, E.C.P.M. (author), Staats, P.G.M. (author)

Objective: Development and validation of a short Observation List of possible early signs of Dementia (OLD) for use in general practice. Design: Stepwise development using reviews of publications and expert consensus. Field study for evaluation of reliability. Validation study (interviews, family forms) using existing valid and reliable measures...

article 2001

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Reduced levels of cholesterol, phospholipids, and fatty acids in cerebrospinal fluid of Alzheimer disease patients are not related to apolipoprotein E4

Mulder, M. (author), Ravid, R. (author), de Kloet, J.E.R. (author), Haasdijk, E.D. (author), Julk, J. (author), van der Boom, J. (author), Havekes, L.M. (author), Gaubius Instituut TNO (author)

Apolipoprotein E4 (apoE4) has been identified as a major risk factor for Alzheimer disease (AD). Previously it has been reported that levels of apoE are reduced in cerebrospinal fluid (CSF) of AD patients. Because it is known that apoE4 affectss plasma lipid metabolism we examined whether the presence of apoE4 might correlate with an altered...

article 1998

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Serum apolipoprotein e level is not increased in Alzheimer's disease: The Rotterdam study

Slooter, A.J.C. (author), de Knijff, P. (author), Hofman, A. (author), Cruts, M. (author), Breteler, M.M.B. (author), van Broeckhoven, C. (author), Havekes, L.M. (author), van Duijn, C.M. (author), Gaubius Instituut TNO (author)

The APOE*4 allele of the apolipoprotein E gene (APOE) is an important risk factor for Alzheimer's disease. It has been suggested that levels of apolipoprotein E (apoE) in plasma are increased in Alzheimer's disease. In this population-based study, we found that serum apoE levels were lower in Alzheimer patients compared to non-demented controls ...

article 1998