Journal of Alzheimer's Disease - Volume 23, issue 1

Authors: Booij, Birgitte Boonstra | Lindahl, Torbjørn | Wetterberg, Peter | Skaane, Nina Voss | Sæbø, Solve | Feten, Guri | Rye, Phil D. | Kristiansen, Lena Iren | Hagen, Nina | Jensen, Marianne | Bårdsen, Ken | Winblad, Bengt | Sharma, Praveen | Lönneborg, Anders

Article Type: Research Article

Abstract: A whole genome screen was performed using oligonucleotide microarray analysis on blood from a large clinical cohort of Alzheimer's disease (AD) patients and control subjects as clinical sample. Blood samples for total RNA extraction were collected in PAXgene tubes, and gene expression analysis performed on the AB1700 Whole Genome Survey Microarrays. When comparing the gene expression of 94 AD patients and 94 cognitive healthy controls, a Jackknife gene selection based method and Partial Least Square Regression (PLSR) was used to develop a disease classifier algorithm, which gives a test score indicating the presence (positive) or absence (negative) of AD. This …algorithm, based on 1239 probes, was validated in an independent test set of 63 subjects comprising 31 AD patients, 25 age-matched cognitively healthy controls, and 7 young controls. This algorithm correctly predicted the class of 55/63 (accuracy 87%), including 26/31 AD samples (sensitivity 84%) and 29/32 controls (specificity 91%). The positive likelihood ratio was 8.9 and the area under the receiver operating characteristic curve (ROC AUC) was 0.94. Furthermore, the algorithm also discriminated AD from Parkinson's disease in 24/27 patients (accuracy 89%). We have identified and validated a gene expression signature in blood that classifies AD patients and cognitively healthy controls with high accuracy and show that alterations specific for AD can be detected distant from the primary site of the disease. Show more

Keywords: Alzheimer's disease, blood, biomarker, diagnostic test, microarray, RNA

DOI: 10.3233/JAD-2010-101518

Citation: Journal of Alzheimer's Disease, vol. 23, no. 1, pp. 109-119, 2011

Authors: Rye, Phil. D. | Booij, Birgitte Boonstra | Grave, Gisle | Lindahl, Torbjørn | Kristiansen, Lena | Andersen, Hilde-Marie | Horndalsveen, Peter O. | Nygaard, Harald A. | Naik, Mala | Hoprekstad, Dagne | Wetterberg, Peter | Nilsson, Christer | Aarsland, Dag | Sharma, Praveen | Lönneborg, Anders

Article Type: Research Article

Abstract: Despite a variety of testing approaches, it is often difficult to make an accurate diagnosis of Alzheimer's disease (AD), especially at an early stage of the disease. Diagnosis is based on clinical criteria as well as exclusion of other causes of dementia but a definitive diagnosis can only be made at autopsy. We have investigated the diagnostic value of a 96-gene expression array for detection of early AD. Gene expression analysis was performed on blood RNA from a cohort of 203 probable AD and 209 cognitively healthy age matched controls. A disease classification algorithm was developed on samples from 208 …individuals (AD = 103; controls = 105) and was validated in two steps using an independent initial test set (n = 74; AD = 32; controls = 42) and another second test set (n = 130; AD = 68; controls = 62). In the initial analysis, diagnostic accuracy was 71.6 ± 10.3%, with sensitivity 71.9 ± 15.6% and specificity 71.4 ± 13.7%. Essentially the same level of agreement was achieved in the two independent test sets. High agreement (24/30; 80%) between algorithm prediction and subjects with available cerebrospinal fluid biomarker was found. Assuming a clinical accuracy of 80%, calculations indicate that the agreement with underlying true pathology is in the range 85%-90%. These findings suggest that the gene expression blood test can aid in the diagnosis of mild to moderate AD, but further studies are needed to confirm these findings. Show more

Keywords: Alzheimer's disease, biomarker, blood, diagnostic test, gene expression, RNA

DOI: 10.3233/JAD-2010-101521

Citation: Journal of Alzheimer's Disease, vol. 23, no. 1, pp. 121-129, 2011

Authors: Pilotto, Alberto | D'Onofrio, Grazia | Benelli, Edoardo | Zanesco, Antonio | Cabello, Ana | Margelí, M. Carmen | Wanche-Politis, Sophia | Seferis, Kostas | Sancarlo, Daniele | Kilias, Dimitrios | on behalf of the HOPE Investigators

Article Type: Research Article

Abstract: Within the frame of the European Commission funded Smart Home for Elderly People (HOPE) Project, relatives/caregivers of 223 Alzheimer's Disease (AD) patients were recruited in Italy, Spain, and Greece for a multicenter international survey on the potential role of Information and Communication Technology system (ICT-systems) for AD patients. A five-minute video on HOPE ICT-systems was shown, and all relatives/caregivers completed a 13-item questionnaire that evaluated the potential role of: A) ICT-systems in improving quality of life, care, and safety; B) devices for monitoring personal movements, medication use, and ambient environmental conditions; C) devices to improve communication, home-based rehabilitation, and reduction …of specific risks; and D) possible agreement in using ICT-systems by AD patients. Relatives/caregivers reported that ICT-systems could be very useful to improve: A) quality of life (66.4%), care (56.1%), and safety (87.0%); B) monitoring bed rest and movements (80.7%), medication use (87.4%), and ambient environmental conditions (85.2%); and C) emergency communication (83.4%). Relatives/caregivers reported that ICT-systems could be significantly more useful for AD patients aged 75–84 than patients aged <75 or ≥85 years (p < 0.0001) and with moderate than mild or severe dementia (p < 0.0001). Relatives/caregivers aged ≥50 years and with low educational level considered ICT-systems more useful than relatives/caregivers aged <50 years (p < 0.0001) and with high educational level (p < 0.0001). In conclusion, relatives/caregivers considered that the HOPE ICT-system could be useful to improve the management of AD patients. Show more

Keywords: Alzheimer's disease, HOPE project, quality of care, quality of life, safety, user-friendly high-technology systems

DOI: 10.3233/JAD-2010-101164

Citation: Journal of Alzheimer's Disease, vol. 23, no. 1, pp. 131-141, 2011

Authors: Frisardi, Vincenza | Imbimbo, Bruno P.

Article Type: Research Article

Abstract: In an aging world, maintaining good health and independence for as long as possible is essential. Instead of hospitalization or institutionalization, the elderly with chronic conditions, especially those with cognitive impairment, can be assisted in their own environment with numerous ‘smart’ devices that support them in their activity of daily living. A “smart home” is a residence equipped with technology that facilitates monitoring of residents to improve quality of life and promote physical independence, as well as to reduce caregiver burden. Several projects worldwide have been conducted, but some ethical and legal issues are still unresolved and, at present, there …is no evidence of the effects of smart homes on health outcomes. Randomized controlled trials are needed to understand the plus and minuses of these projects, but this will only be possible with a widespread proliferation and penetration of smart homes in the social network. Show more

Keywords: Alzheimer's disease, domotics, information and communication technology, obtrusiveness, quality of life, smart homes

DOI: 10.3233/JAD-2010-101599

Citation: Journal of Alzheimer's Disease, vol. 23, no. 1, pp. 143-146, 2011

Authors: Moon, Minho | Choi, Jin Gyu | Nam, Dong Woo | Hong, Hyun-Seok | Choi, Young-Ju | Oh, Myung Sook | Mook-Jung, Inhee

Article Type: Research Article

Abstract: Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by cognitive deficits, neuroinflammation, and loss of neurons. Recently, it has been shown that ghrelin, a 28 amino acid peptide hormone produced from the stomach and hypothalamus, has been reported as a potential therapeutic agent for several neurological disorders, including Parkinson's disease (PD), stroke, epilepsy, multiple sclerosis, and spinal cord injury. Here we determined the effects of ghrelin on memory impairments and neuropathological changes in an AD mouse model induced by intrahippocampal injection of amyloid-β oligomers (AβO). We report that ghrelin: 1) rescues memory deficits in mice injected with AβO in …the hippocampus; 2) decreases AβO-induced microgliosis in hippocampus; 3) attenuates hippocampal neuronal loss mediated by AβO; 4) prevents AβO-associated synaptic degeneration including cholinergic fiber loss. Taken together, our findings demonstrate that ghrelin can ameliorate AβO-induced cognitive impairment associated with neuroinflammation and neuronal loss. These results suggest that ghrelin may be a promising therapeutic agent for the treatment of AD. Show more

Keywords: Alzheimer's disease, amyloid-β oligomer, cognitive impairment, ghrelin, neurodegeneration, neuroinflammation

DOI: 10.3233/JAD-2010-101263

Citation: Journal of Alzheimer's Disease, vol. 23, no. 1, pp. 147-159, 2011

Authors: Zilkova, Monika | Zilka, Norbert | Kovac, Andrej | Kovacech, Branislav | Skrabana, Rostislav | Skrabanova, Michaela | Novak, Michal

Article Type: Research Article

Abstract: Neurofibrillary degeneration and neuronal loss represent key pathological hallmarks of Alzheimer's disease (AD). It has been demonstrated that the decrease of total neuronal numbers correlates with the presence of neurofibrillary degeneration in AD brain. In order to unravel the mechanism leading to the cell death in AD, we developed a stably transfected human neuroblastoma cellular model with doxycycline-regulatable expression of AD truncated tau protein (AT tau, 151-391 4R). Cells expressing the longest tau isoform (Tau 40) were used as a control. We found that more than 80% of the total amount of AT tau and Tau 40 were phosphorylated. Strikingly, …both AT tau and Tau 40 reduced the metabolic activity of the cells in a time-dependent manner (p < 0.0001) suggesting that tau overexpression slows down cell proliferation. However, AT tau showed significantly higher toxicity than Tau 40 (p < 0.0001), which indicates that truncation leads to a toxic gain of function. The analysis of the type of the cell death revealed the characteristic features of apoptosis such as cell shrinkage, nuclear, and DNA fragmentation. However, we did not find either the activation of executive caspase (caspase-3) or the caspase cleavage products (PARP and fodrin). These results show that posttranslationally modified truncated tau protein induces caspase-3-independent apoptosis-like programmed cell death, a phenomenon we term tauoptosis. Show more

Keywords: Alzheimer's disease, apoptosis, cell death, cell model, truncated tau protein

DOI: 10.3233/JAD-2010-101434

Citation: Journal of Alzheimer's Disease, vol. 23, no. 1, pp. 161-169, 2011

Authors: Breitner, John C.S.

Article Type: Article Commentary

DOI: 10.3233/JAD-2010-101351

Citation: Journal of Alzheimer's Disease, vol. 23, no. 1, pp. 171-172, 2011

Article Type: Other

DOI: 10.3233/JAD-2010-101603

Citation: Journal of Alzheimer's Disease, vol. 23, no. 1, pp. 173-175, 2011