Journal of Alzheimer's Disease - Volume 53, issue 3

Authors: Zimmerer, Vitor C. | Wibrow, Mark | Varley, Rosemary A.

Article Type: Research Article

Abstract: Background: Language change can be a valuable biological marker of overall cognitive change in Alzheimer’s disease (AD) and other forms of dementia. Previous reports have described increased use of language formulas in AD, i.e., combinations likely processed in a holistic manner. Words that commonly occur together are more likely to become a formula. Objective: To determine if frequency of co-occurrence as one indicator for formulaic language can distinguish people with probable AD from controls and if variables are sensitive to time post-symptom onset. Methods: We developed the Frequency in Language Analysis Tool (FLAT), which indicates …degrees of formulaicity in an individual language sample. The FLAT accomplishes this by comparing individual language samples to co-occurrence data from the British National Corpus (BNC). Our analysis also contained more conventional language variables in order to assess novel contributions of the FLAT. We analyzed data from the Pitt Corpus, which is part of DementiaBank. Results: Both conventional and co-occurrence variables were able to distinguish AD and control groups. According to co-occurrence data, people with probable AD produced more formulaic language than controls. Only co-occurrence variables correlated with disease progression. Discussion: Frequency of word co-occurrences is one indicator for formulaicity and a valuable contribution to characterizing language change in AD. Show more

Keywords: Alzheimer’s disease, disease progression, language, verbal behavior

DOI: 10.3233/JAD-160099

Citation: Journal of Alzheimer's Disease, vol. 53, no. 3, pp. 1145-1160, 2016

Authors: Hawkins, Kara M. | Sergio, Lauren E.

Article Type: Research Article

Abstract: Background: Many neuroimaging parameters have demonstrated utility as biomarkers in preclinical AD, including resting-state functional connectivity in the default mode network. However, neuroimaging is not a practical, cost effective screening instrument. Objective: Here we investigate the relationship between performance on a cognitive-motor integration assessment and alterations in resting-state functional connectivity in an at-risk population. Methods: Three groups of ten adults (young: mean age = 26.6 ± 2.7, low AD risk: mean age = 58.7 ± 5.6, and high AD risk: mean age = 58.5 ± 6.9) performed a simple cognitive-motor integration task using a dual-touchscreen laptop and also underwent functional magnetic …resonance imaging at rest. Results: We found poorer cognitive-motor integration performance in high AD risk participants, as well as an association with lower resting-state functional connectivity in this group. Conclusion: These findings provide novel insight into underlying AD-related brain alterations associated with a behavioral assessment that can be easily administered clinically. Show more

Keywords: Aging, ApoE4, dementia, functional magnetic resonance imaging, geriatric assessment, population at risk, psychomotor performance

DOI: 10.3233/JAD-151137

Citation: Journal of Alzheimer's Disease, vol. 53, no. 3, pp. 1161-1172, 2016

Authors: Gao, Hui-ling | Li, Cheng | Nabeka, Hiroaki | Shimokawa, Tetsuya | Wang, Zhan-You | Cao, Ya-ming | Matsuda, Seiji

Article Type: Research Article

Abstract: The pathological hallmarks of Alzheimer’s disease (AD) include amyloid-β (Aβ) accumulation, neurofibrillary tangle formation, synaptic dysfunction, and neuronal loss. The present study was performed to investigate the protective effects and mechanism of action of a prosaposin-derived 18-mer peptide (PS18: LSELIINNATEELLIKGL) on mice hippocampal progenitor cell proliferation, neurogenesis, and memory tasks after intracerebroventricular injection of Aβ1–42 peptide. Seven days after Aβ1–42 injection, significant proliferation of hippocampal progenitor cells and memory impairment were evident. Two weeks after Aβ1–42 peptide injection, elevated numbers of surviving 5-bromo-2-deoxyuridine cells and newly formed neurons were detected. Treatment with PS18 attenuated these effects evoked …by Aβ1–42 . Our data indicate that treatment with PS18 partially attenuated the increase in hippocampal neurogenesis caused by Aβ1–42 -induced neuroinflammation and prevented memory deficits associated with increased numbers of activated glial cells. We observed an increase in ADAM10 and decreases in BACE1, PS1/2, and AβPP protein levels, suggesting that PS18 enhances the nonamyloidogenic AβPP cleavage pathway. Importantly, our results further showed that PS18 activated the PI3K/Akt pathway, phosphorylated GSK-3α/β, and, as a consequence, exerted a neuroprotective effect. In addition, PS18 showed a protective effect against Aβ1–42 -induced neurotoxicity via suppression of the caspase pathway; upregulation of Bcl-2; downregulation of BAX, attenuating mitochondrial damage; and inhibition of caspase-3. These findings suggest that PS18 may provide a valuable therapeutic strategy for the treatment of progressive neurodegenerative diseases, such as AD. Show more

Keywords: Aβ1–42 peptide, Akt/GSK-3α/β, Alzheimer’s disease, apoptosis, neurogenesis, prosaposin

DOI: 10.3233/JAD-160093

Citation: Journal of Alzheimer's Disease, vol. 53, no. 3, pp. 1173-1192, 2016

Authors: Biella, Gloria | Fusco, Federica | Nardo, Emanuele | Bernocchi, Ottavia | Colombo, Alessio | Lichtenthaler, Stefan F. | Forloni, Gianluigi | Albani, Diego

Article Type: Research Article

Abstract: The neuropathological hallmarks of Alzheimer’s disease (AD) are extracellular plaques built up by the accumulation of the amyloid-β protein precursor (AβPP)-derived peptide β (Aβ), and intracellular tangles of hyperphosphorylated tau protein. Sirtuin 2 (SIRT2) is a member of the sirtuin family, featuring conserved enzymes with deacetylase activity and involved in several cell molecular pathways. We investigated the importance of SIRT2 inhibition in AD. We inhibited SIRT2 by small molecules (AGK-2, AK-7) and examined AβPP metabolism in H4-SW neuroglioma cells overexpressing AβPP and two AD transgenic mouse models (3xTg-AD and APP23). The in vitro studies suggested that the inhibition of …SIRT2 reduced Aβ production; in vivo data showed an improvement of cognitive performance in the novel object recognition test, and an effect on AβPP proteolytic processing leading to a reduction of soluble β-AβPP and an increase of soluble α-AβPP protein. In 3xTg-AD mice, we noticed that total tau protein level rose. Overall, our pre-clinical data support a role for SIRT2 inhibition in the improvement of cognitive performance and the modulation of molecular mechanisms relevant for AD, thus deserving attention as possible therapeutic strategy. Show more

Keywords: AK-7, Alzheimer’s disease, amyloid-β protein precursor processing, Sirtuin 2, tau

DOI: 10.3233/JAD-151135

Citation: Journal of Alzheimer's Disease, vol. 53, no. 3, pp. 1193-1207, 2016

Authors: Salem, Haitham | Rocha, Natalia Pessoa | Colpo, Gabriela Delevati | Teixeira, Antonio Lucio

Article Type: Research Article

Abstract: To date, there is no definitive treatment for Alzheimer’s disease (AD). The realm of stem cells is very promising in regenerative medicine, particularly neurodegenerative disorders. Various types of stem cells have been used in multiple trials on AD models, trying to find an innovative management of this disease. In this systematic review, we trace the published preclinical and clinical data throughout the last decade, to show how much knowledge we gained so far in this field and the future perspectives of stem cells in AD treatment.

Keywords: Alzheimer’s disease, clinical trails, neurodegenerative diseases, preclinical trials, stem cells

DOI: 10.3233/JAD-160250

Citation: Journal of Alzheimer's Disease, vol. 53, no. 3, pp. 1209-1230, 2016

Article Type: Other

DOI: 10.3233/JAD-160547

Citation: Journal of Alzheimer's Disease, vol. 53, no. 3, pp. 1231-1235, 2016