The Latest Articles on Alzheimer Disease
Our staff editors continue to share exciting, interesting, and thought-provoking reading material in the recommended articles series.
This week, we would like to share several latest articles on Alzheimer Disease.
Title: Deep learning-based classification of healthy aging controls, mild cognitive impairment and Alzheimer's disease using fusion of MRI-PET imaging
Authors: V.P. Subramanyam Rallabandi, Krishnamoorthy Seetharaman
Type: Research Article
Automated detection of dementia stage using multimodal imaging modalities will be helpful for improving the clinical diagnosis. In this study, we develop the Inception-ResNet wrapper model in differentiating the healthy controls (HC), mild cognitive impairment (MCI), and Alzheimer’s disease (AD) using conjoint magnetic resonance imaging (MRI) and positron emission tomography (PET) scans. We use T1-weighted MR and PET images of individuals aged between 42 and 95 years, including HC, MCI and AD patients. We first perform 3D tissue segmentation of MR images after skull striping. The atlas-based segmented MR image tissue is fused with PET image. Then we transform PET images from RGB to HSI color space and apply fusion of MRI with PET images using two-dimensional Fourier and discrete wavelet transform (DWT) and then reconstruct the MR-PET fused image using inverse Fourier and DWT methods. After the fusion of MRI and PET imaging modalities, we used 60% training, 20% for validation and the remaining 20% as a test set using various convolutional neural networks. We found the proposed model as the best classifier with an accuracy of 95.5%, 94.1% and 95.9% in classifying HC vs MCI, MCI vs AD and AD vs HC respectively when compared to the existing methods. We conclude that the proposed deep learning model has potential in automated classification of healthy and dementia stages using combined MRI and PET modalities with good performance.
Access this article: https://doi.org/10.1016/j.bspc.2022.104312
Title: Involvement of calcium ions in amyloid-β-induced lamin fragmentation
Authors: Md. Selim Hossain, Vijay Sankar Ramasamy, Il-Seon Park
Type: Research Article
Amyloid-β (Aβ) peptide, the main pathogenic peptide in Alzheimer's disease, has been shown to induce an increase in cytoplasmic calcium concentration (CCC). In the current study, we explored the cytotoxic signal transduction pathway in 42-amino-acid Aβ (Aβ42)-treated HeLa cells in relation to the increase in CCC. The increase in CCC was prominent in cells treated twice with oligomeric Aβ42. We previously showed that double treatment also promoted Aβ-induced lamin fragmentation (AILF), which appears to be mediated by cathepsin L. Apoptotic caspase activation was a downstream event of AILF. The Ca2+ chelator BAPTA-AM suppressed cell death, cathepsin L activation, AILF, and caspase activation in Aβ-treated cells. These results indicate that Aβ42 induces an increase in CCC, which is an event upstream of the cytotoxic processes. The products of AILF are different from those produced by other cell death-inducing agents, such as staurosporine, which induces caspase-6-mediated lamin fragmentation (CMLF). CMLF was unaffected by BAPTA-AM and was not detected in cells treated with Aβ42, indicating that Aβ42 peptide induced a specific cytotoxic pathway involving AILF via increased CCC. We confirmed that the same processes (except caspase activation) operated in Aβ42-treated neuroblastoma SH-SY5Y cells.
Access this article: https://doi.org/10.1016/j.bbamcr.2022.119383
Title: An MnO2-ZIF-67 immobilized acetylcholinesterase method for acetylcholinesterase activity assay and inhibitor screening from Inula macrophylla based on capillary electrophoresis
Authors: Jia Liu, Rui Ma, Wei Ha, Hai-Xia Zhang, Yan-Ping Shi
Type: Research Article
The inhibition of acetylcholinesterase (AChE) from decomposing acetylcholine (ACh) is regarded as a common therapeutic strategy for Alzheimer's disease (AD). Screening AChE inhibitors is of great significance for AD treatment. In this work, AChE was physically absorbed on the synthesized MnO2-ZIF-67 through electrostatic interaction for the first time, and the fabricated MnO2-ZIF-67 immobilized AChE coupled with capillary electrophoresis (CE) was applied to screening AChE inhibitor. The established MnO2-ZIF-67 immobilized AChE with excellent pH, thermal and organic solvents tolerance stability was evaluated by Ellman's method. Huperzine A was used as model inhibitor to investigate the inhibition kinetics of the immobilized AChE, which possess the feasibility and applicability for its inhibitor screening. The screening mechanism of AChE inhibitor was based on the Ellman's method and measured by the changes of 5-thio-2-nitrobenzoic acid (TNB), which was produced by the reaction of thiocholine (TCh) with 5,5-dithiobis-(2-nitrobenzoic acid) (DTNB). Benefiting from the advantages of convenience and high sensitivity, the proposed platform was employed to screen AChE inhibitors from 11 compounds isolated from Inula macrophylla, and macrophyllic acid A (compound 1), dibutyl phthalate (compound 2) exhibited strong AChE inhibitory activity. Thus, this work not only provides a promising platform for monitoring AChE activity, but also holds great potential for the further exploration of active components with AChE inhibitory activity from Inula macrophylla.
Access this article: https://doi.org/10.1016/j.talanta.2022.124025
Title: Prevention of microgliosis halts early memory loss in a mouse model of Alzheimer's disease
Authors: Mandy S.J. Kater, Christiaan F.M. Huffels, Takuya Oshima, Niek S. Renckens, Jinte Middeldorp, Erik W.G.M. Boddeke, August B. Smit, Bart J.L. Eggen, Elly M. Hol, Mark H.G. Verheijen
Type: Research Article
Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by cognitive decline, the neuropathological formation of amyloid-beta (Aβ) plaques and neurofibrillary tangles. The best cellular correlates of the early cognitive deficits in AD patients are synapse loss and gliosis. In particular, it is unclear whether the activation of microglia (microgliosis) has a neuroprotective or pathological role early in AD. Here we report that microgliosis is an early mediator of synaptic dysfunction and cognitive impairment in APP/PS1 mice, a mouse model of increased amyloidosis. We found that the appearance of microgliosis, synaptic dysfunction and behavioral impairment coincided with increased soluble Aβ42 levels, and occurred well before the presence of Aβ plaques. Inhibition of microglial activity by treatment with minocycline (MC) reduced gliosis, synaptic deficits and cognitive impairments at early pathological stages and was most effective when provided preventive, i.e., before the onset of microgliosis. Interestingly, soluble Aβ levels or Aβ plaques deposition were not affected by preventive MC treatment at an early pathological stage (4 months) whereas these were reduced upon treatment at a later stage (6 months). In conclusion, this study demonstrates the importance of early-stage prevention of microgliosis on the development of cognitive impairment in APP/PS1 mice, which might be clinically relevant in preventing memory loss and delaying AD pathogenesis.
Access this article: https://doi.org/10.1016/j.bbi.2022.10.009
Title: Air pollution exposure during pregnancy and childhood, APOE ε4 status and Alzheimer polygenic risk score, and brain structural morphology in preadolescents
Authors: Esmée Essers, Anne-Claire Binter, Alexander Neumann, Tonya White, Silvia Alemany, Mònica Guxens
Type: Research Article
Air pollution exposure is associated with impaired neurodevelopment, altered structural brain morphology in children, and neurodegenerative disorders. Differential susceptibility to air pollution may be influenced by genetic features.
To evaluate whether the apolipoprotein E (APOE) genotype or the polygenic risk score (PRS) for Alzheimer's Disease (AD) modify the association between air pollution exposure during pregnancy and childhood and structural brain morphology in preadolescents.
We included 1186 children from the Generation R Study. Concentrations of fourteen air pollutants were calculated at participants’ home addresses during pregnancy and childhood using land-use-regression models. Structural brain images were collected at age 9–12 years to assess cortical and subcortical brain volumes. APOE status and PRS for AD were examined as genetic modifiers. Linear regression models were used to conduct single-pollutant and multi-pollutant (using the Deletion/Substitution/Addition algorithm) analyses with a two-way interaction between air pollution and each genetic modifier.
Higher pregnancy coarse particulate matter (PMcoarse) and childhood polycyclic aromatic hydrocarbons exposure was differentially associated with larger cerebral white matter volume in APOE ε4 carriers compared to non-carriers (29,485 mm3 (95% CI 6,189; 52,781) and 18,663 mm3 (469; 36,856), respectively). Higher pregnancy PMcoarse exposure was differentially associated with larger cortical grey matter volume in children with higher compared to lower PRS for AD (19436 mm3 (825, 38,046)).
APOE status and PRS for AD possibly modify the association between air pollution exposure and brain structural morphology in preadolescents. Higher air pollution exposure is associated with larger cortical volumes in APOE ε4 carriers and children with a high PRS for AD. This is in line with typical brain development, suggesting an antagonistic pleiotropic effect of these genetic features (i.e., protective effect in early-life, but neurodegenerative effect in adulthood). However, we cannot discard chance findings. Future studies should evaluate trajectorial brain development using a longitudinal design.
Access this article: https://doi.org/10.1016/j.envres.2022.114595