Journal of Alzheimer's Disease - Volume 35, issue 2

Authors: Porzoor, Afsaneh | Macreadie, Ian G.

Article Type: Review Article

Abstract: The major molecules associated with Alzheimer's disease, the phosphorylated protein tau and the 42 amino acid peptide, amyloid-β (Aβ), have recently been analyzed in yeast. These yeast studies have provided major new insights into the effects of tau and Aβ and, at the same time, offered new approaches to rapidly search for chemicals that may be involved in prevention of Alzheimer's disease. The following review summarizes the role of yeast and its contribution in Alzheimer's disease research, and highlights important studies that have been conducted in this model organism.

Keywords: Alzheimer's disease, amyloid-β, Candida glabrata, Pichia pastoris, Saccharomyces cerevisiae, Schizosaccharomyces pombe, tau

DOI: 10.3233/JAD-122035

Citation: Journal of Alzheimer's Disease, vol. 35, no. 2, pp. 217-225, 2013

Authors: Bruner, Emiliano | Jacobs, Heidi I.L.

Article Type: Research Article

Abstract: Clinical grade Alzheimer's disease (AD) is only described in humans. Recent imaging studies in early AD patients showed that the parietal areas display the most prominent metabolic impairments. So far, neuroimaging studies have not been able to explain why the medial parietal regions possess this hub characteristic in AD. Paleoneurological and neuroanatomical studies suggest that our species, Homo sapiens, has a unique and derived organization of the parietal areas, which are involved in higher cognitive functions. Combining evidence from neuroimaging, paleontology, and comparative anatomy, we suggest that the vulnerability of the parietal lobe to neurodegenerative processes may be associated with …the origin of our species. The species-specific parietal morphology in modern humans largely influenced the brain spatial organization, and it involved changes in vascularization and energy management, which may underlie the sensitivity of these areas to metabolic impairment. Metabolic constraints and anatomical evolutionary changes in the medial parietal regions of modern humans may be important in early AD onset. Taking into account the species-specific adaptations of the modern human parietal areas and their association with AD, we hypothesize that AD can be the evolutionary drawback of the specialized structure of our parietal lobes. The cognitive advantage is associated with increased sensitivity to neurodegenerative processes which, being limited to the post-reproductive period, have a minor effect on the overall genetic fitness. The changes of energy requirements associated with form and size variations at the parietal areas may support the hypothesis of AD as a metabolic syndrome. Show more

Keywords: Aging, brain evolution, dementia, Homo sapiens, metabolism, paleoneurology

DOI: 10.3233/JAD-122299

Citation: Journal of Alzheimer's Disease, vol. 35, no. 2, pp. 227-240, 2013

Authors: Vermeiren, Angelique P.A. | Bosma, Hans | Visser, Pieter-Jelle | Zeegers, Maurice P. | Graff, Caroline | Ewers, Michael | Frisoni, Giovanni B. | Frölich, Lutz | Hampel, Harald | Jones, Roy W. | Kehoe, Patrick G. | Lenoir, Hermine | Minthon, Lennart | Nobili, Flavio M. | Olde Rikkert, Marcel | Rigaud, Anne-Sophie | Scheltens, Philip | Soininen, Hilkka | Spiru, Luiza | Tsolaki, Magda | Wahlund, Lars-Olof | Vellas, Bruno | Wilcock, Gordon | Elias-Sonnenschein, Lyzel S. | Verhey, Frans R.J.

Article Type: Short Communication

Abstract: We assessed the interaction between the APOE ε4 allele and education level in the etiology of Alzheimer's disease (AD) among memory clinic patients from the multicenter DESCRIPA study. Subjects (n = 544) were followed for 1 to 5 years. We used Cox's stratified survival modeling, adjusted for age, gender, and center. APOE ε4 predicted the onset of AD-type dementia in middle (HR 3.45 95% CI 1.79–6.65, n = 222) and high (HR 3.67 95% CI 1.36–9.89, n = 139) but not in low educated subjects (HR 0.81, 95% CI 0.38–1.72, n = 183). This suggests that mechanisms in developing Alzheimer-type …dementia may differ between educational groups that raises questions related to Alzheimer-type dementia prevention. Show more

Keywords: APOE ε4, cohort study, dementia, education, multicenter study, mild cognitive impairment, socio-economic status

DOI: 10.3233/JAD-122182

Citation: Journal of Alzheimer's Disease, vol. 35, no. 2, pp. 241-246, 2013

Authors: Benke, Thomas | Delazer, Margarete | Sanin, Günter | Schmidt, Helena | Seiler, Stephan | Ransmayr, Gerhard | Dal-Bianco, Peter | Uranüs, Margarete | Marksteiner, Josef | Leblhuber, Friedrich | Kapeller, Peter | Bancher, Christian | Schmidt, Reinhold | On behalf of the PRODEM Study Group

Article Type: Research Article

Abstract: Background: Few studies have investigated in detail which factors influence activities of daily (ADL) in Alzheimer’s disease (AD). Objective: To assess the influence of cognitive, gender, and other factors on ADL in patients with mild to moderate AD. Methods: This study is part of the Prospective Registry on Dementia in Austria (PRODEM) project, a multicenter dementia research project. A cohort of 221 AD patients (130 females; means: age 76 years, disease duration 34.4 months, MMSE 22.3) was included in a cross-sectional analysis. Everyday abilities were assessed with the Disability Assessment for Dementia scale, and cognitive functions …with the CERAD plus neuropsychological test battery. Two models of multiple linear regressions were performed to find factors predicting functional decline, one entering demographical and disease related factors, and a joint model combining demographical and disease variables with neuropsychological scores. Results: Non-cognitive factors explained 18%, whereas the adding of neuropsychological variables explained 39% of variance. Poor figural and verbal memory, constructional abilities, old age, longer disease duration, depression, and male gender were independent risk factors for reduced ADL. Instrumental and basic ADL were predicted by similar factors, except gender (predicting only instrumental ADL) and phonological fluency (predictor of basic ADL). Conclusion: In addition to demographical factors, disease duration, and depression, neuropsychological variables are valuable predictors of the functional status in AD in an early disease stage. Show more

Keywords: Alzheimer's disease, cognitive impairment, functional abilities, gender

DOI: 10.3233/JAD-122383

Citation: Journal of Alzheimer's Disease, vol. 35, no. 2, pp. 247-252, 2013

Authors: Watts, Amber S. | Loskutova, Natalia | Burns, Jeffrey M. | Johnson, David K.

Article Type: Research Article

Abstract: Metabolic syndrome (MetS) is a cluster of risk factors (i.e., abdominal obesity, hypertension, dyslipidemia, glucose and insulin dysregulation) that is associated with cardiovascular disease, diabetes, and dementia. Recent studies addressing the association of MetS with cognitive performance and risk for dementia report mixed results. An important step in clarifying these conflicting results is determining whether cognition is influenced by the effects of individual MetS components versus the additive effects of multiple components. We assessed the effect of MetS on cognitive performance and decline over two years in 75 cases of early Alzheimer's disease (AD) and 73 healthy older adult controls …in the Brain Aging Project. Using factor analytic techniques, we compared the effect of a combined MetS factor to the effect of individual MetS components on change in attention, verbal memory, and mental status. In healthy controls, a combined MetS factor did not significantly predict cognitive performance, though higher insulin predicted poorer cognitive performance outcomes. In the AD group, higher scores on a combined MetS factor predicted better cognitive outcomes. Our findings suggest that MetS does not have the same association with cognitive decline in healthy older adults and those with early AD. We suggest that individual MetS components should not be evaluated in isolation and that careful methodological approaches are needed to understand the timing and non-linear relationships among these components over time. Show more

Keywords: Alzheimer's disease, cognitive decline, factor analysis, metabolic syndrome

DOI: 10.3233/JAD-121168

Citation: Journal of Alzheimer's Disease, vol. 35, no. 2, pp. 253-265, 2013

Authors: Faivre, Emilie | Hölscher, Christian

Article Type: Research Article

Abstract: Type 2 diabetes mellitus has been identified as a risk factor for Alzheimer's disease (AD). We have previously shown that glucose-dependent insulinotropic polypeptide (GIP) analogues that originally have been developed to treat diabetes have neuroprotective effects in the brains of the APPswe/PS1ΔE9 mouse model of AD. In a previous study, the analogue D-Ala2 GIP intraperitoneally (i.p.) in 12 months old animals, an age that represents early phase AD, D-Ala2 GIP improved memory in wild type (WT) mice and rescued the cognitive decline of 12 months old AβPP/PS1 mice. Synapse numbers and synaptic plasticity was also protected. Importantly, the amyloid plaque …load in the cortex was reduced. In the present study, we tested D-Ala2 GIP in 19 months old AβPP/PS1 mice or littermate controls to find out if the drug may have protective effects even at an advanced stage of AD. Mice were injected for 21 days at 25 nmol/kg i.p. once daily. Interestingly, the age-related reduction of synaptic numbers in the DG and cortex was prevented in WT control mice. D-Ala2 GIP facilitated synaptic plasticity in AβPP/PS1 and WT mice and reduced the number of amyloid plaques and activated microglia in the cortex of AβPP/PS1 mice. The results show that D-Ala2 GIP not only has protective but also regenerative properties in the brain of aged WT mice, and on key biomarkers found in AD in AβPP/PS1 mice. This suggests that novel GIP analogues may have beneficial effects in non-demented aged people and perhaps even in AD patients even when the disease is further progressed. Show more

Keywords: Growth factor, incretins, insulin, neuroprotection

DOI: 10.3233/JAD-121888

Citation: Journal of Alzheimer's Disease, vol. 35, no. 2, pp. 267-283, 2013

Authors: Jelic, Vesna | Hagman, Göran | Yamamoto, Natsuko Goto | Teranishi, Yasuhiro | Nishimura, Takeshi | Winblad, Bengt | Pavlov, Pavel F.

Article Type: Research Article

Abstract: Previous findings demonstrated an altered pattern of amyloid-β protein precursor (AβPP) expression in platelets of Alzheimer's disease (AD) patients compared with either healthy control subjects or patients with non-Alzheimer-type dementia. In an attempt to explore the diagnostic potential of platelet AβPP metabolism, we have generated monoclonal antibodies directed to the N-terminal part of AβPP. We have observed two different antibody recognition patterns of AβPP: one resembling previously described 130 kDa and 105 kDa species and a novel AβPP 115 kDa form. This form was significantly increased in platelets of the mild cognitive impairment and AD group as compared to control …subjects. The abundance of AβPP 115 kDa species correlated with the previously described AβPP 130/105 kDa ratio as well as with Mini-Mental State Examination score. Despite the inability of these particular monoclonal antibodies to recognize native forms of AβPP, identification of a new AβPP isoform in platelets as a potential AD biomarker can provide an additional tool for the development of a reliable diagnostic test to detect preclinical stages of AD. Show more

Keywords: Alzheimer's disease, amyloid-β protein precursor, biomarker, platelets

DOI: 10.3233/JAD-122122

Citation: Journal of Alzheimer's Disease, vol. 35, no. 2, pp. 285-295, 2013

Authors: Slachevsky, Andrea | Budinich, Marilu | Miranda-Castillo, Claudia | Núñez-Huasaf, Javier | Silva, Jaime R. | Muñoz-Neira, Carlos | Gloger, Sergio | Jimenez, Oscar | Martorell, Bernardo | Delgado, Carolina

Article Type: Research Article

Abstract: Background: Caring for a person with dementia is associated with well-documented increases in burden and distress and decreases in mental health and wellbeing. Studies assessing burden in caregivers of patients with dementia and its determinants are scarce in Latin America. Objective: The main objective of this study was to assess the extent and the determinants of burden in informal primary caregivers of patients with dementia in Chile. Methods: A descriptive study was conducted using clinically validated scales to assess dementia characteristics and to measure caregiver variables. Family socio-demographic characteristics and functional status, patient functional dependency and …behavioral disturbances, and caregiver psychiatric morbidity were analyzed as independent variables to determine caregiver burden. Results: Two hundred and ninety-two informal caregivers were included. There were more female (80%) than male caregivers, consisting mainly of daughters and spouses of the patients. Severe burden was reported in 63% of the caregivers, and 47% exhibited psychiatric morbidity. Burden was associated with caregiver psychiatric distress, family dysfunction, severity of neuropsychiatric symptoms and functional disability, but neither patient age, gender, nor socioeconomic status impacted burden. Conclusion: Our results underscore the importance of assessing the consequences of dementia in both caregivers and patients in order to evaluate the real biopsychosocial impact of dementia, as well as the importance of planning appropriate and effective public health interventions in Latin American countries. In addition, interventions targeting caregiver psychological distress, caregiver familial dysfunction, patient neuropsychiatric disorders, and patient functional disability could potentially diminish caregiver burden. Show more

Keywords: Alzheimer's disease, caregiver, dementia, dependency, dependency burden, general health questionnaire, mental health, neuropsychiatric inventory, psychological distress, Zarit burden interview

DOI: 10.3233/JAD-122086

Citation: Journal of Alzheimer's Disease, vol. 35, no. 2, pp. 297-306, 2013

Authors: Shahim, Pashtun | Bochem, Andrea E. | Mattsson, Niklas | Lautner, Ronald | Blennow, Kaj | Hovingh, G. Kees | Motazacker, M. Mahdi | Zetterberg, Henrik

Article Type: Research Article

Abstract: Tangier disease (TD) is a rare genetic disorder caused by mutations in the ATP-binding cassette transporter A1 (ABCA1) gene, which results in impaired cellular cholesterol efflux and high-density lipoprotein cholesterol deficiency. Animal and in vitro studies indicate that ABCA1 is involved in the production of amyloid-β (Aβ), a pivotal protein in Alzheimer's disease. We here examined whether plasma Aβ levels are altered in TD patients. Plasma from 5 TD patients and 5 controls were analyzed for Aβ1-40 , Aβ1-42 , AβX-40 , and AβX-42 but no differences were found. In conclusion, loss of ABCA1 function may not have any …profound effect on Aβ metabolism in humans, at least not in the periphery, as reflected by plasma Aβ levels. Show more

Keywords: Alzheimer's disease, amyloid-β, biological markers, plasma, Tangier disease

DOI: 10.3233/JAD-122425

Citation: Journal of Alzheimer's Disease, vol. 35, no. 2, pp. 307-312, 2013

Authors: Piscopo, Paola | Rivabene, Roberto | Galimberti, Daniela | Crestini, Alessio | Talarico, Giuseppina | Vanacore, Nicola | Scarpini, Elio | Bruno, Giuseppe | Confaloni, Annamaria

Article Type: Research Article

Abstract: Plasma progranulin (PGRN) levels constitute a potentially invaluable biomarker for neurodegenerative diseases including frontotemporal lobar degeneration (FTLD) and, perhaps, Alzheimer's disease (AD). We assessed plasma PGRN levels in 107 AD patients, 36 FTLD patients, and 107 controls. We found that, in female AD patients, there is a positive correlation between PGRN levels and age. Although no significant differences were found between patients and controls, we observed higher levels in females compared to males; in AD patients, a positive correlation between PGRN levels and age was observed in females. In conclusion, our data suggest that PGRN may not be a good …biomarker for AD; moreover, gender may influence the plasma PGRN levels of AD patients. Show more

Keywords: Alzheimer's disease, gender, plasma, progranulin

DOI: 10.3233/JAD-121606

Citation: Journal of Alzheimer's Disease, vol. 35, no. 2, pp. 313-318, 2013