Alzheimer's disease immunization strategies : a review of current research

Scholarly project (M.S.)

Intelligent sensing technologies for the diagnosis, monitoring and therapy of alzheimer’s disease:A systematic review

Alzheimer’s disease is a lifelong progressive neurological disorder. It is associated with high disease management and caregiver costs. Intelligent sensing systems have the capability to provide context-aware adaptive feedback. These can assist Alzheimer’s patients with, continuous monitoring, functional support and timely therapeutic interventions for whom these are of paramount importance. This review aims to present a summary of such systems reported in the extant literature for the management of Alzheimer’s disease. Four databases were searched, and 253 English language articles were identified published between the years 2015 to 2020. Through a series of filtering mechanisms, 20 articles were found suitable to be included in this review. This study gives an overview of the depth and breadth of the efficacy as well as the limitations of these intelligent systems proposed for Alzheimer’s. Results indicate two broad categories of intelligent technologies, distributed systems and self-contained devices. Distributed systems base their outcomes mostly on long-term monitoring activity patterns of individuals whereas handheld devices give quick assessments through touch, vision and voice. The review concludes by discussing the potential of these intelligent technologies for clinical practice while highlighting future considerations for improvements in the design of these solutions for Alzheimer’s disease

Monoaminergic Neuropathology in Alzheimer's disease

Acknowledgments This work was supported by The Croatian Science Foundation grant. no. IP-2014-09-9730 (“Tau protein hyperphosphorylation, aggregation, and trans-synaptic transfer in Alzheimer’s disease: cerebrospinal fluid analysis and assessment of potential neuroprotective compounds”) and European Cooperation in Science and Technology (COST) Action CM1103 (“Stucture-based drug design for diagnosis and treatment of neurological diseases: dissecting and modulating complex function in the monoaminergic systems of the brain”). PRH is supported in part by NIH grant P50 AG005138.Peer reviewedPostprin

Cognitive performance in multiple system atrophy

The cognitive performance of a group of patients with multiple system atrophy (MSA) of striato-nigral predominance was compared with that of age and IQ matched control subjects, using three tests sensitive to frontal lobe dysfunction and a battery sensitive to memory and learning deficits in Parkinson's disease and dementia of the Alzheimer type. The MSA group showed significant deficits in all three of the tests previously shown to be sensitive to frontal lobe dysfunction. Thus, a significant proportion of patients from the MSA group failed an attentional set-shifting test, specifically at the stage when an extra-dimensional shift was required. They were also impaired in a subject-ordered test of spatial working memory. The MSA group showed deficits mostly confined to measures of speed of thinking, rather than accuracy, on the Tower of London task. These deficits were seen in the absence of consistent impairments in language or visual perception. Moreover, the MSA group showed no significant deficits in tests of spatial and pattern recognition previously shown to be sensitive to patients early in the course of probable Alzheimer's disease and only a few patients exhibited impairment on the Warrington Recognition Memory Test. There were impairments on other tests of visual memory and learning relative to matched controls, but these could not easily be related to fundamental deficits of memory or learning. Thus, on a matching-to-sample task the patients were impaired at simultaneous but not delayed matching to sample, whereas difficulties in a pattern-location learning task were more evident at its initial, easier stages. The MSA group showed no consistent evidence of intellectual deterioration as assessed from their performance on subtests of the Wechsler Adult Intelligence Scale (WAIS) and the National Adult Reading Test (NART). Consideration of individual cases showed that there was some heterogeneity in the pattern of deficits in the MSA group, with one patient showing no impairment, even in the face of considerable physical disability. The results show a distinctive pattern of cognitive deficits, unlike those previously seen using the same tests in patients with Parkinson's and Alzheimer's diseases, and suggesting a prominent frontal-lobe-like component. The implications for concepts of 'subcortical' dementia and 'fronto-striatal' cognitive dysfunction are considered

The effectiveness of physical rehabilitation in the enhancement of proprioceptive and cognitive aspects on Alzheimer disease patients.

Based on the Alzheimer Disease (AD) prevention and slowing down, this study has shown interest in evaluating the effects of Global Postural Re-education (GPR) on the cognitiveness of individuals with AD. OBJECTIVE: It is important to verify that by modifying and improving postural attitudes, a better concentration of cognitions in older people is achieved, increases self-awareness and proprioception. MATERIALS AND METHODS: This research study is based on an experimental design where participated 135 subjects with AD. It lasted 6 months, with pre-post tests executed before and after the period of treatment. RESULTS: The therapy had a significant effect on the Mini Mental State Examination (MMSE), Geriatric Depression Scale (GDS), Quality of life in AD (QoL-AD), Barthel Index (BI), Neuropsychiatric Inventory (NPI) and Tinetti Scale scores (TS) compared to the ones of group factor. In the findings of post-hoc analysis it was observed: the improvement of treatment variables, MMSE scores, GDS, QoL -AD and BI (p corrected by Bonferroni <0.005 in all cases). Nonetheless, the improvement was also observed from the first month of therapy in TS scores and NPI (p corrected by Bonferroni <0.005 in all cases). CONCLUSIONS: This study confirms the validity of the GPR proposal on the cognitiveness of individuals with AD.Actividad Física y DeporteMedicinaTerapia y Rehabilitació

Oxidative stress, mitochondrial abnormalities and proteins deposition: multitarget approaches in Alzheimer's disease

Alzheimer diseases (AD) is a multifactorial pathology characterized by a complex etiology. The hallmarks of AD, such as Aβ deposits in senile plaque and neurofibrillary tangles (NFT), are strongly intertwined with reactive oxygen species (ROS)production and oxidative stress (OS),which are considered the common effectors of the cascade of degenerative events. An increasing body of evidence reveals that both mitochondrial abnormalities and metal accumulations synergistically act as major producers of ROS, thus contributing to neuronal toxicity. Consequently, the detrimental role of ROS production together with the neurodegenerative events involved in AD has been widely investigated as new potential therapeutic strategies. This review will concisely summarize the link between OS and the hallmarks of AD, emphasizing on their strong correlation with neurodegenerative events and elucidating the pivotal role of ROS in AD pathology. Furthermore, through this review, we will provide a short account of some of the efforts, challenges and opportunities in developing multitarget drugs by addressing ROS production, metal accumulation and protein depositions

Probing Amyloid-beta protein structure and dynamics with a selective antibody

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder. The AD brain is characterized by significant neuronal loss and accumulation of insoluble fibrillar amyloid-β protein (Aβ) plaques and tau protein neurofibrillary tangles in the brain. However, over the last decade, many studies have shown that the neurodegenerative effect of Aβ may in fact be caused by various soluble oligomeric forms as opposed to the insoluble fibrils. Furthermore, the data suggest that a pre-fibrillar aggregated form, termed protofibrils, mediates direct neurotoxicity, and triggers a robust neuroinflammatory response. Antibodies targeting the various conformation of Aβ are important therapeutic agents to prevent the progression of AD. We have generated conformationally-selective monoclonal antibody St. Louis (mAbSL) that selectively targets Aβ42 protofibrils compared to Aβ42 monomers and fibrils. The development aspects of these antibodies include the cloning of HC and LC variable fragments into the plasmid vector, transfection of the plasmids into 293 F cells, collection of the supernatant and purification using Protein A or protein G affinity chromatography. Sequencing of the heavy and light chain variable regions for multiple antibodies identified sequence characteristics that may impart conformational selectivity to the antibodies. Thus, I have successfully developed, expressed, and characterized these conformationally selective antibodies using various ELISA formats. Exploration of Aβ42 aggregation in the presence a selective (mAbSL 113) and a non-selective antibody (mAb Ab 513) using spectroscopic and microscopic techniques is quintessential to looking at the effect of these antibodies on Aβ42 monomer aggregation and protofibril dynamics. It yielded a unique inhibitory mechanism on Aβ42 monomer aggregation offered by mAbSL antibodies. Aβ42 protofibril dynamics were prominently altered in the presence of mAbSL 113 with an insoluble complex formation by the antibody at low sub-stoichiometric molar ratios. We focused on accurately determining the conformational epitope of our developed antibodies on Aβ42 protofibrils. The conformational epitope on Aβ42 protofibril was detected using a monoclonal antibody in various experimental formats like antibody competition ELISA, HDX-MS, and FPOP analysis. Our findings demonstrated new insights into monoclonal antibodies that target AD progression

In vivo mapping of cholinergic terminals in normal aging, Alzheimer's disease, and Parkinson's disease

To map presynaptic cholinergic terminal densities in normal aging (n = 36), Alzheimer's disease (AD) (n = 22), and Parkinson's disease (PD) (n = 15), we performed single-photon emission computed tomography using [ 123 I]iodoben-zovesamicol (IBVM), an in vivo marker of the vesicular acetylcholine transporter. We used coregistered positron emission tomography with [ 18 F]fluorodexyglucose for metabolic assessment and coregistered magnetic resonance imaging for atrophy assessment. In controls (age, 22–91 years), cortical IBVM binding declined only 3.7% per decade. In AD, cortical binding correlated inversely with dementia severity. In mild dementia, binding differed according to age of onset, but metabolism did not. With an onset age of less than 65 years, binding was reduced severely throughout the entire cerebral cortex and hippocapus (about 30%), but with an onset age of 65 years or more, binding reductions were restricted to temporal cortex and hippocampus. In PD without dementia, binding was reduced only in parietal and occipital cortex, but demented PD subjects had extensive cortical binding decreases similar to early-onset AD. We conclude that cholinergic neuron integrity can be monitored in living AD and PD patients, and that it is not so devastated in vivo as suggested by postmortem choline acetylransferase activity (50–80%).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/50361/1/410400309_ftp.pd