Journal of Alzheimer's Disease - Volume 36, issue 3

Authors: Landré, Lionel | Sava, Alina-Alexandra | Krainik, Alexandre | Lamalle, Laurent | Krolak-Salmon, Pierre | Chainay, Hanna

Article Type: Research Article

Abstract: Emotional material tends to be better retrieved in memory than neutral material. This emotional enhancement of memory may be related to the attentional effects of the amygdala's response to emotional stimuli. Because early neuropathological changes in Alzheimer's disease involve the amygdala and the hippocampus, it has been suggested that this effect is impaired in patients. However inconsistent results have been reported. The goal of our study was to evaluate the effects of emotion on picture recognition in patients affected by Alzheimer's disease, and to explore the link between this effect and the degree of amygdalar and hippocampal atrophy. Mild Alzheimer's …disease patients (n = 15) and control participants (n = 20) performed an Old/New recognition task using pictures of negative, neutral, and positive emotional valence. Automated segmentation of their high-resolution T1 MRI scans was performed in order to obtain amygdalar and hippocampal volumes. Correlation analyses were then performed between volumetric data, memory, and the emotional effect on memory. An effect of emotion on memory was found for control participants (with positive items being better recognized than neutral and negative ones), with no correlation between this effect and medial temporal volumes, and a significant correlation between overall recognition scores and hippocampal volumes. Conversely, no emotional effect on memory was found across the group of patients; however, significant correlations were found between the loss of this effect and amygdalar and hippocampal volumes. These results tend to confirm a link between the loss of emotional effect on memory and neuropathological change in medial temporal structures during the course of Alzheimer's disease. Show more

Keywords: Alzheimer's disease, amygdala, emotions, hippocampus, memory, MRI

DOI: 10.3233/JAD-130170

Citation: Journal of Alzheimer's Disease, vol. 36, no. 3, pp. 535-544, 2013

Authors: Iuliano, Luigi | Pacelli, Antonio | Ciacciarelli, Marco | Zerbinati, Chiara | Fagioli, Sabrina | Piras, Fabrizio | Orfei, Maria Donata | Bossù, Paola | Pazzelli, Floriana | Serviddio, Gaetano | Caltagirone, Carlo | Spalletta, Gianfranco

Article Type: Research Article

Abstract: Polyunsaturated fatty acids (PUFA) of the n-3 series have been linked to brain physiology and cognitive decline, but little is known about the other components of the complex fatty acids category. Here, we compared 30 molecular species pertaining to saturated, monounsaturated, polyunsaturated, and trans fatty acids, measured in plasma by gas chromatography, in 14 patients with a diagnosis of amnestic single domain mild cognitive impairment (aMCI), 30 patients with mild Alzheimer's disease (AD), and 30 healthy controls (HC). As no participants showed neuroimaging evidence of cerebrovascular disease, patients could be considered as purely neurodegenerative. We found differences in specific components …of almost all fatty acid classes except n-3-polyunsaturated fatty acids. Compared with HC, aMCI and AD patients had higher levels of arachidic (C20:0), erucic (C22:1, n-9), and vaccenic acid (C18:1, n-9) and lower levels of cerotic (C26:0) and linoleic acid (C18:2, n-6). In particular, level of linoleic acid decreased and level of mead acid increased progressively from HC to aMCI to AD patients, and they were also inversely correlated in AD and aMCI patients. In conclusion, we found a previously unrecognized linoleic acid deficiency in the early phase of neurodegeneration that was strongly supported by an increased, compensatory mead acid level. These findings suggest the importance of creating new dietary manipulation strategies to counteract disease progression. Show more

Keywords: Alzheimer's disease, fatty acids, linoleic acid, neurodegeneration

DOI: 10.3233/JAD-122224

Citation: Journal of Alzheimer's Disease, vol. 36, no. 3, pp. 545-553, 2013

Authors: Do, Tuan Minh | Bedussi, Beatrice | Chasseigneaux, Stéphanie | Dodacki, Agnès | Yapo, Cédric | Chacun, Hélène | Scherrmann, Jean-Michel | Farinotti, Robert | Bourasset, Fanchon

Article Type: Research Article

Abstract: The influx of amyloid-β peptide (Aβ) across the blood-brain barrier is partly mediated by the receptor for advanced glycation end products (RAGE). But other transporters, like Oatp (organic anion transporter polypeptide, SLC21) transporters, could also be involved. We used in situ brain perfusion to show that rosuvastatin and taurocholate, two established Oatp1a4 substrates, decreased (5-fold) the Clup of [3 H]Aβ while L-thyroxine increased it (5.5-fold). We demonstrated an interaction between Aβ and Oatp1a4 by co-immunoprecipitation and western blotting experiments, supporting the hypothesis that the rosuvastatin- and taurocholate-sensitive transporter was Oatp1a4. In conclusion, our results suggest that, in mice, the …brain uptake of Aβ is partly mediated by Oatp1a4 and that L-thyroxine may play a crucial role in the inhibition of brain Aβ clearance. Show more

Keywords: Alzheimer's disease, amyloid-β peptide, blood-brain barrier, in situ brain perfusion, L-thyroxine, Oatp1a4, rosuvastatin

DOI: 10.3233/JAD-121891

Citation: Journal of Alzheimer's Disease, vol. 36, no. 3, pp. 555-561, 2013

Authors: Duits, Flora H. | Kester, Maartje I. | Scheffer, Peter G. | Blankenstein, Marinus A. | Scheltens, Philip | Teunissen, Charlotte E. | van der Flier, Wiesje M.

Article Type: Research Article

Abstract: In this longitudinal study we investigated the effect of apolipoprotein E (APOE) genotype on the relation between cognitive decline and cerebrospinal fluid (CSF) F2 -isoprostanes, the reference marker for oxidative stress. Twenty non-demented subjects, 58 mild cognitive impairment (MCI) patients, and 63 Alzheimer's disease (AD) patients with measurements of CSF F2 -isoprostanes at two time points (with a mean interval of 2.0 ± 1.1 years) and known APOE genotype were included. Mean clinical follow-up time was 3.9 ± 2.4 years. For change in F2 -isoprostanes over time and associations with Mini-Mental State Examination scores, age- and gender-adjusted linear mixed models …were used. Analyses were done for APOE ε4 carriers and non-carriers separately. In APOE ε4 carriers, annual change in F2 -isoprostane levels appeared larger than in APOE ε4 non-carriers (β[SE] 2.5[0.5], p < 0.001 versus 1.8[0.5], p < 0.01). In addition, increase in F2 -isoprostanes was associated with further cognitive decline in APOE ε4 carriers (p < 0.05), but not in non-carriers (p = 0.28). Our results reiterate the importance of oxidative stress in neurodegeneration, especially in APOE ε4 carrying patients. Future studies should focus on the possibility of increased vulnerability to oxidative damage in APOE ε4 carriers. Show more

Keywords: Alzheimer's disease, apolipoprotein E ε4, cerebrospinal fluid biomarkers, F2-isoprostanes, longitudinal study, oxidative stress

DOI: 10.3233/JAD-122227

Citation: Journal of Alzheimer's Disease, vol. 36, no. 3, pp. 563-570, 2013

Authors: Vikarunnessa, Sheikh | Weiner, Myron F. | Vega, Gloria Lena

Article Type: Research Article

Abstract: Background: Centenarians with normal cognitive function have a “longevity phenotype” characterized by large low-density lipoproteins (LDL) and high-density lipoproteins (HDL) and low incidence of metabolic syndrome, hypertension, and cognitive impairment. Alzheimer’s disease (AD) is associated with a number of cardiovascular risk factors, but it is not known if they have or lack the “longevity phenotype”. Objective: The study was designed to determine LDL size and body fat content and distribution in subjects with mild cognitive impairment (MCI) and AD. Results: Fifty-eight persons with MCI or AD (cases) and 42 control subjects of similar age had measurement …of LDL size and lipoprotein lipids after a 12 h fast and analysis of body composition by dual x-ray absorptiometry. Cases had small LDL size more often than controls (73% versus 66%) associated with significantly higher triglycerides, lower HDL cholesterol, and higher triglyceride/HDL cholesterol ratio (p ⩽ 0.02). Cases with large LDL had a better lipoprotein profile than those with small LDL. Cases and controls had similar percent body fat, fat index, and lean mass index. Forty-seven percent of cases and 39% of controls were obese. Conclusion: The prevalence of small LDL phenotype in MCI and AD cases contrasts with the “longevity phenotype” reported for centenarians with preserved cognitive function. The small LDL phenotype is an atherogenic lipoprotein profile found in metabolic syndrome, type 2 diabetes, and insulin resistance. It is now also reported in persons with MCI and AD. Show more

Keywords: Atherogenic dyslipidemia, longevity phenotype, small LDL

DOI: 10.3233/JAD-130443

Citation: Journal of Alzheimer's Disease, vol. 36, no. 3, pp. 571-575, 2013

Authors: Palmer, Jennifer C. | Tayler, Hannah M. | Love, Seth

Article Type: Research Article

Abstract: Alzheimer's disease (AD) patients have reduced cerebral blood flow. This precedes dementia and may contribute to its progression. In mice that overexpress amyloid-β protein precursor, cerebral blood flow declines before the development of plaques or cognitive abnormalities. In the brain, endothelin-1 (ET-1) is a locally acting vasoconstrictor, produced in neurons by endothelin-converting enzyme (ECE)-2 and in endothelial cells by ECE-1. Both ECEs are also capable of cleaving amyloid-β (Aβ). We previously showed ECE-2 and ET-1 to be elevated in postmortem temporal cortex from AD patients, and ECE-2 expression and ET-1 release to be upregulated by Aβ42 in vitro. We …have now studied isolated leptomeningeal blood vessels from postmortem brains and found that although ECE-1 level is reduced, ECE-1 activity and ET-1 level are significantly elevated in AD vessels. This is specific to AD as there is no specific change in vascular dementia vessels. In primary cultures of human brain endothelial cells, both Aβ40 and Aβ42 caused a significant increase in ET-1 release, the increase being particularly pronounced with Aβ40 . In view of previous studies implicating free radicals in the endothelial dysfunction caused by Aβ40 , we examined whether Aβ-mediated ET-1 release could be prevented by the antioxidant superoxide dismutase. Addition of superoxide dismutase to cells exposed to Aβ40 prevented the increase in the concentration of ET-1. Our findings indicate that cerebral vasoconstriction induced by Aβ results in part from a free radical-mediated increase in ECE-1 activity and ET-1 production. Show more

Keywords: Alzheimer's disease, cerebral blood flow, endothelin-1, free radicals, vascular dysfunction

DOI: 10.3233/JAD-130383

Citation: Journal of Alzheimer's Disease, vol. 36, no. 3, pp. 577-587, 2013

Authors: Peters, Owen M. | Shelkovnikova, Tatyana | Tarasova, Tatiana | Springe, Signe | Kukharsky, Michail S. | Smith, Gaynor A. | Brooks, Simon | Kozin, Sergey A. | Kotelevtsev, Yury | Bachurin, Sergey O. | Ninkina, Natalia | Buchman, Vladimir L.

Article Type: Research Article

Abstract: Dimebon has been tested as a potential modifier of Alzheimer's disease (AD), resulting in mixed clinical trial outcomes. Originally utilized as an antihistamine, Dimebon was later found to ameliorate AD symptoms in initial human trials. Although subsequent trials have reportedly failed to replicate these finding, there is a growing body of evidence that Dimebon might be neuroprotective in certain models of neurodegeneration. The precise mechanism by which Dimebon is thought to act in AD is unclear, though changes in receptor activity, mitochondria function, and autophagy activity have been proposed. It is thus necessary to test Dimebon in transgenic animal model …systems to determine if and how the drug affects development and manifestation of pathology, and which pathogenic processes are altered. In the present study we treated mice harboring five familial mutations associated with hereditary AD (5xFAD line) with a chronic regime of Dimebon. The compound was not found to improve the general health or motor behavior of these mice, nor prevent accumulation of Aβ peptides in the brain. Modest changes in response to an anxiogenic task were, however, detected, suggesting Dimebon might improve behavioral abnormalities and cognition in disease in a mechanism independent of protecting against amyloidosis. Show more

Keywords: Alzheimer's disease, dimebolin, latrepirdine, tauopathy, therapeutics, transgenic mice

DOI: 10.3233/JAD-130071

Citation: Journal of Alzheimer's Disease, vol. 36, no. 3, pp. 589-596, 2013

Authors: Jefferson, Angela L. | Lambe, Susan | Romano, Raymond R. | Liu, Dandan | Islam, Fareesa | Kowall, Neil

Article Type: Research Article

Abstract: Background: Alzheimer’s disease (AD) rates are higher among African Americans than in other racial or ethnic groups. However, Black elders participate in research at lower rates than Whites. Objective: The present study aimed to: (1) implement an informational protocol for African Americans elders and their loved ones about the benefits of clinical research and brain donation program participation in AD, and (2) quantitatively assess changes in knowledge, attitudes, and trust. Methods: Participants included 52 African American participants from the Boston University Alzheimer’s Disease Center research registry (74 ± 8 years, 83% female) and 11 loved ones. …Registry participants completed a pre- and post-group survey assessing brain donation knowledge, factors influencing brain donation, attitudes about medical research, and trust in medical researchers. Results: There were no significant changes in mean scores between the pre- and post-group surveys. However, post-group outcomes revealed that 69% of participants shared details from the protocol with loved ones, 27% expressed an interest in joining Center-sponsored studies, and 10% indicated an interest in changing their brain donation status. Conclusion: The informational protocol implemented in this study is an effective method to encourage family discussions about brain donation and increase interest in other AD research studies. Longitudinal follow-up is necessary to assess the long-term implications of these groups on participation in a brain donation program. Show more

Keywords: Black populations, brain autopsy, cognitive impairment, research enthusiasm

DOI: 10.3233/JAD-130287

Citation: Journal of Alzheimer's Disease, vol. 36, no. 3, pp. 597-606, 2013

Authors: Baird, Raymond

Article Type: Book Review

DOI: 10.3233/JAD-130841

Citation: Journal of Alzheimer's Disease, vol. 36, no. 3, pp. 607-607, 2013

Article Type: Other

DOI: 10.3233/JAD-130564

Citation: Journal of Alzheimer's Disease, vol. 36, no. 3, pp. 609-611, 2013