Journal of Alzheimer's Disease - Volume 41, issue 1

Authors: Olde Rikkert, Marcel G.M. | Verhey, Frans R. | Sijben, John W.C. | Bouwman, Femke H. | Dautzenberg, Paul L.J. | Lansink, Mirian | Sipers, Walther M.W. | van Asselt, Dieneke Z.B. | van Hees, Anneke M.J. | Stevens, Martijn | Vellas, Bruno | Scheltens, Philip

Article Type: Research Article

Abstract: Background: Studies on the systemic availability of nutrients and nutritional status in Alzheimer’s disease (AD) are widely available, but the majority included patients in a moderate stage of AD. Objective: This study compares the nutritional status between mild AD outpatients and healthy controls. Methods: A subgroup of Dutch drug-naïve patients with mild AD (Mini-Mental State Examination (MMSE) ≥20) from the Souvenir II randomized controlled study (NTR1975) and a group of Dutch healthy controls were included. Nutritional status was assessed by measuring levels of several nutrients, conducting the Mini Nutritional Assessment (MNA® ) questionnaire and through anthropometric …measures. Results: In total, data of 93 healthy cognitively intact controls (MMSE 29.0 [23.0–30.0]) and 79 very mild AD patients (MMSE = 25.0 [20.0–30.0]) were included. Plasma selenium (p < 0.001) and uridine (p = 0.046) levels were significantly lower in AD patients, with a similar trend for plasma vitamin D (p = 0.094) levels. In addition, the fatty acid profile in erythrocyte membranes was different between groups for several fatty acids. Mean MNA screening score was significantly lower in AD patients (p = 0.008), but not indicative of malnutrition risk. No significant differences were observed for other micronutrient or anthropometric parameters. Conclusion: In non-malnourished patients with very mild AD, lower levels of some micronutrients, a different fatty acid profile in erythrocyte membranes and a slightly but significantly lower MNA screening score were observed. This suggests that subtle differences in nutrient status are present already in a very early stage of AD and in the absence of protein/energy malnutrition. Show more

Keywords: Alzheimer's disease, fatty acids, healthy volunteers, micronutrients, nutritional status, protein-energy malnutrition

DOI: 10.3233/JAD-131892

Citation: Journal of Alzheimer's Disease, vol. 41, no. 1, pp. 261-271, 2014

Authors: Tajes, Marta | Eraso-Pichot, Abel | Rubio-Moscardó, Fanny | Guivernau, Biuse | Ramos-Fernández, Eva | Bosch-Morató, Mònica | Guix, Francesc Xavier | Clarimón, Jordi | Miscione, Gian Pietro | Boada, Mercé | Gil-Gómez, Gabriel | Suzuki, Toshiharu | Molina, Henrik | Villà-Freixa, Jordi | Vicente, Rubén | Muñoz, Francisco J.

Article Type: Research Article

Abstract: Amyloid-β peptide (Aβ) aggregates induce nitro-oxidative stress, contributing to the characteristic neurodegeneration found in Alzheimer's disease (AD). One of the most strongly nitrotyrosinated proteins in AD is the triosephosphate isomerase (TPI) enzyme which regulates glycolytic flow, and its efficiency decreased when it is nitrotyrosinated. The main aims of this study were to analyze the impact of TPI nitrotyrosination on cell viability and to identify the mechanism behind this effect. In human neuroblastoma cells (SH-SY5Y), we evaluated the effects of Aβ42 oligomers on TPI nitrotyrosination. We found an increased production of methylglyoxal (MG), a toxic byproduct of the inefficient nitro-TPI …function. The proapoptotic effects of Aβ42 oligomers, such as decreasing the protective Bcl2 and increasing the proapoptotic caspase-3 and Bax, were prevented with a MG chelator. Moreover, we used a double mutant TPI (Y165F and Y209F) to mimic nitrosative modifications due to Aβ action. Neuroblastoma cells transfected with the double mutant TPI consistently triggered MG production and a decrease in cell viability due to apoptotic mechanisms. Our data show for the first time that MG is playing a key role in the neuronal death induced by Aβ oligomers. This occurs because of TPI nitrotyrosination, which affects both tyrosines associated with the catalytic center. Show more

Keywords: Alzheimer's disease, amyloid, apoptosis, methylglyoxal, 3-nitrotyrosine, triose-phosphate isomerase

DOI: 10.3233/JAD-131685

Citation: Journal of Alzheimer's Disease, vol. 41, no. 1, pp. 273-288, 2014

Authors: Evangelisti, Elisa | Zampagni, Mariagioia | Cascella, Roberta | Becatti, Matteo | Fiorillo, Claudia | Caselli, Anna | Bagnoli, Silvia | Nacmias, Benedetta | Cecchi, Cristina

Article Type: Research Article

Abstract: Increasing evidence indicates that interaction of amyloid-β peptide (Aβ) with the cell membrane is a primary step in Alzheimer's disease (AD) neurotoxicity. In particular, it has been demonstrated that lipid rafts are key sites of Aβ production, aggregation, and interaction with the cell membrane. In this study we show that Aβ42 oligomers are recruited to lipid rafts, leading to plasma membrane perturbation and Ca2+ dyshomeostasis in primary fibroblasts from familial AD patients bearing APPVal717Ile, PS-1Leu392Val, or PS-1Met146Leu gene mutations. In contrast, a moderate increase in membrane cholesterol content precluded the interaction of Aβ42 oligomers with the plasma …membrane and resulting cell damage. Moreover, the recruitment of amyloid assemblies to lipid raft domains of cholesterol-depleted fibroblasts was significantly increased, thus triggering an earlier and sharper increase in intracellular Ca2+ levels and plasma membrane permeabilization. Our findings suggest a protective role for raft cholesterol against amyloid toxicity in AD. Show more

Keywords: Aβ42-GM1 colocalization, Alzheimer's disease fibroblasts, calcium dysregulation, lipid rafts, membrane cholesterol, membrane permeabilization, prion

DOI: 10.3233/JAD-131406

Citation: Journal of Alzheimer's Disease, vol. 41, no. 1, pp. 289-300, 2014

Authors: Alonso, Ruth | Pisa, Diana | Marina, Ana Isabel | Morato, Esperanza | Rábano, Alberto | Carrasco, Luis

Article Type: Research Article

Abstract: Alzheimer's disease is a progressive neurodegenerative disorder that leads to dementia mainly among the elderly. This disease is characterized by the presence in the brain of amyloid plaques and neurofibrillary tangles that provoke neuronal cell death, vascular dysfunction, and inflammatory processes. In the present work, we have analyzed the existence of fungal infection in Alzheimer's disease patients. A proteomic analysis provides compelling evidence for the existence of fungal proteins in brain samples from Alzheimer's disease patients. Furthermore, PCR analysis reveals a variety of fungal species in these samples, dependent on the patient and the tissue tested. DNA sequencing demonstrated that …several fungal species can be found in brain samples. Together, these results show that fungal macromolecules can be detected in brain from Alzheimer's disease patients. To our knowledge these findings represent the first evidence that fungal infection is detectable in brain samples from Alzheimer's disease patients. The possibility that this may represent a risk factor or may contribute to the etiological cause of Alzheimer's disease is discussed. Show more

Keywords: Alzheimer's disease, brain proteomics, fungal DNA, fungal PCR, fungal infection

DOI: 10.3233/JAD-132681

Citation: Journal of Alzheimer's Disease, vol. 41, no. 1, pp. 301-311, 2014

Authors: van der Flier, Wiesje M. | Pijnenburg, Yolande A.L. | Prins, Niels | Lemstra, Afina W. | Bouwman, Femke H. | Teunissen, Charlotte E. | van Berckel, Bart N.M. | Stam, Cornelis J. | Barkhof, Frederik | Visser, Pieter Jelle | van Egmond, Evan | Scheltens, Philip

Article Type: Research Article

Abstract: Since its opening in 2000, patient care and research go hand in hand at the Alzheimer center of the VU University Medical Center, both organized in such a way that they mutually strengthen each other. Our mission is to give patients a voice by lifting the stigma on dementia, to find new diagnostic and treatment strategies, and, ultimately, to cure diseases that cause dementia. Our healthcare pathway is uniquely designed to accommodate all necessary investigations for the diagnostic work-up of dementia in one day (one-stop shop). A second unique feature is that research has been fully integrated in the healthcare …pathway. The resulting Amsterdam Dementia Cohort now includes over 4000 patients, and for the majority of these, we have MRI, EEG, blood (serum, plasma), DNA, and CSF available. The Amsterdam Dementia Cohort forms the basis of much of our research, which focuses on four major research lines: 1) variability in manifestation, 2) early diagnosis, 3) vascular factors, and 4) interventions. By answering research questions closely related to clinical practice, the results of our research can be looped back to improve clinical work-up for our patients. Show more

Keywords: Alzheimer's disease, dementia, diagnosis, investigations, mild cognitive impairment, work-up

DOI: 10.3233/JAD-132306

Citation: Journal of Alzheimer's Disease, vol. 41, no. 1, pp. 313-327, 2014

Article Type: Other

DOI: 10.3233/JAD-140091

Citation: Journal of Alzheimer's Disease, vol. 41, no. 1, pp. 329-330, 2014