BOX-COUNTING ANALYSIS OF MICROGLIA FORM IN SCHIZOPHRENIA, ALZHEIMER'S DISEASE AND AFFECTIVE DISORDER

Fractals ◽  
2008 ◽  
Vol 16 (02) ◽  
pp. 103-107 ◽  
Author(s):  
A. L. KARPERIEN ◽  
H. F. JELINEK ◽  
A. M. BUCHAN
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Affective Disorder ◽  
Objective Measure ◽  
Fractal Dimensions ◽  
Normal Function ◽  
Cell Diameter ◽  
Functional Requirements ◽  
Box Counting ◽  
Microglia Morphology

In pathological brain, a variety of morphological forms exist that reflect differences in functional requirements. To better understand microglia function in neurological disease, it is important to identify and quantify microglia morphology associated with specific neuropathologies. Traditional feature parameters such as area or cell diameter are not sufficient. In this study microglia were quantified by the box-counting fractal dimension (DB). One hundred and four cells from post-mortem tissue were analyzed comprising cells of controls, Alzheimer's disease, schizophrenia and affective disorder. The DBwas significantly different from the control (1.36) compared to schizophrenia (1.41), Alzheimer's disease (1.41) and affective disorder (1.43) with p < 0.01. Thus fractal analysis provides a useful quantitative and objective measure of microglial form associated with normal function and diverse neuropathology. The distribution of fractal dimensions associated with microglia structure and activation with disease progression also differs, suggesting a different etiology for these diseases.

scholarly journals Fractal analysis of neuroimaging: comparison between control patients and patients with the presence of Alzheimer’s disease

2022 ◽  
Vol 2159 (1) ◽  
pp. 012011
Author(s):  
J Villamizar ◽  
L Uribe ◽  
A Cerquera ◽  
E Prada ◽  
D Prada ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Fractal Dimension ◽  
Medical Physics ◽  
Fractal Dimensions ◽  
Behavioral Disorder ◽  
Box Counting ◽  
Positron Emission ◽  
Coronary Diseases ◽  
The One

Abstract Alzheimer’s disease is a neurodegenerative cognitive, affective, and behavioral disorder aligned to the aging process and other coronary diseases. To contribute to the early diagnosis of the disease, a neuroimaging treatment is implemented through a preprocessing to subsequently calculate the fractal dimension associated with these images in order to propose an alternative to the one proposed in medical physics through positron emission tomography. In this work, a comparative analysis is made of a previous work using the Box Counting methodology versus the calculation of the fractal dimension by means of software developed by the researchers based on the same method. The differences between the fractal dimensions of the neuroimages of control patients and patients with the presence of the disease are maintained showing a lower value of fractal dimension in patients with the disease due to the physical deterioration of the brain.

The Involvement of Post-Translational Modifications in Alzheimer's Disease

2018 ◽  
Vol 15 (4) ◽  
pp. 313-335 ◽  
Author(s):  
Serena Marcelli ◽  
Massimo Corbo ◽  
Filomena Iannuzzi ◽  
Lucia Negri ◽  
Fabio Blandini ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Modification ◽  
Neurodegenerative Disorder ◽  
Amyloid Β ◽  
Normal Function ◽  
Ageing Population ◽  
Covalent Bonds ◽  
Post Translational Modifications ◽  
Related Proteins

Background: Alzheimer's disease (AD) is a neurodegenerative disorder recognized as the most common cause of chronic dementia among the ageing population. AD is histopathologically characterized by progressive loss of neurons and deposits of insoluble proteins, primarily composed of amyloid-β pelaques and neurofibrillary tangles (NFTs). Methods: Several molecular processes contribute to the formation of AD cellular hallmarks. Among them, post-translational modifications (PTMs) represent an attractive mechanism underlying the formation of covalent bonds between chemical groups/peptides to target proteins, which ultimately result modified in their function. Most of the proteins related to AD undergo PTMs. Several recent studies show that AD-related proteins like APP, Aβ, tau, BACE1 undergo post-translational modifications. The effect of PTMs contributes to the normal function of cells, although aberrant protein modification, which may depend on many factors, can drive the onset or support the development of AD. Results: Here we will discuss the effect of several PTMs on the functionality of AD-related proteins potentially contributing to the development of AD pathology. Conclusion: We will consider the role of Ubiquitination, Phosphorylation, SUMOylation, Acetylation and Nitrosylation on specific AD-related proteins and, more interestingly, the possible interactions that may occur between such different PTMs.

scholarly journals Centro de Día para Enfermos de Alzheimer en Benavente. *** Day Care Centre for people with alzheimer’s disease in Benavente.

2018 ◽  
Author(s):  
Rubén García Rubio ◽  
Sonsoles Vela Navarro
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Reinforced Concrete ◽  
Day Care ◽  
Retaining Walls ◽  
Functional Requirements ◽  
Care Centre ◽  
Social Force ◽  
Horizon Line ◽  
Day Care Centre

Una fuerza social que se manifiesta, un estrato que emerge, una cueva que mira … Un nuevo Centro de Día para Enfermos de Alzheimer en Benavente (Zamora) cuyos requerimientos funcionales y diálogo con el contexto se materializan en una nueva línea de horizonte. Un estrato habitado que dialoga con el contexto a la vez que de elemento semienterrado para prolongar sus muros de contención y dotar al hormigón armado del protagonismo de la obra***A social force that appears, a stratum that emerges, a cave that looks at... A new Day Care Centre for People with Alzheimer’s Disease in Benavente (Zamora) whose functional requirements and dialogue with the context are materialized on a new horizon line. An inhabited stratum that converses with the context as a half-buried element extends its retaining walls and allows the reinforced concrete to provide the character of the building.  

scholarly journals Enhanced Auditory Steady-State Response Using an Optimized Chirp Stimulus-Evoked Paradigm

Sensors ◽  
2019 ◽  
Vol 19 (3) ◽  
pp. 748
Author(s):  
Xiaoya Liu ◽  
Shuang Liu ◽  
Dongyue Guo ◽  
Yue Sheng ◽  
Yufeng Ke ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Practice ◽  
Steady State ◽  
Affective Disorder ◽  
Healthy Subjects ◽  
Signal To Noise Ratio ◽  
Mental Diseases ◽  
40 Hz

Objectives: It has been reported recently that gamma measures of the electroencephalogram (EEG) might provide information about the candidate biomarker of mental diseases like schizophrenia, Alzheimer’s disease, affective disorder and so on, but as we know it is a difficult issue to induce visual and tactile evoked responses at high frequencies. Although a high-frequency response evoked by auditory senses is achievable, the quality of the recording response is not ideal, such as relatively low signal-to-noise ratio (SNR). Recently, auditory steady-state responses (ASSRs) play an essential role in the field of basic auditory studies and clinical uses. However, how to improve the quality of ASSRs is still a challenge which researchers have been working on. This study aims at designing a more comfortable and suitable evoked paradigm and then enhancing the quality of the ASSRs in healthy subjects so as to further apply it in clinical practice. Methods: Chirp and click stimuli with 40 Hz and 60 Hz were employed to evoke the gamma-ASSR respectively, and the sound adjusted to 45 dB sound pressure level (SPL). Twenty healthy subjects with normal-hearing participated, and 64-channel EEGs were simultaneously recorded during the experiment. Event-related spectral perturbation (ERSP) and SNR of the ASSRs were measured and analyzed to verify the feasibility and adaptability of the proposed evoked paradigm. Results: The results showed that the evoked paradigm proposed in this study could enhance ASSRs with strong feasibility and adaptability. 1) ASSR waves in time domain indicated that 40 Hz stimuli could significantly induce larger peak-to-peak values of ASSRs compared to 60 Hz stimuli (p < 0.01**); ERSP showed that obvious ASSRs were obtained at each lead for both 40 Hz and 60 Hz, as well as the click and chirp stimuli. 2) The SNR of the ASSRs were –3.23 ± 1.68, –2.44 ± 2.90, –4.66 ± 2.09, and –3.53 ± 3.49 respectively for 40 Hz click, 40 Hz chirp, 60 Hz click and 60 Hz chirp, indicating the chirp stimuli could induce significantly better ASSR than the click, and 40 Hz ASSRs had the higher SNR than 60 Hz (p < 0.01**). Limitation: In this study, sample size was small and the age span was not large enough. Conclusions: This study verified the feasibility and adaptability of the proposed evoked paradigm to improve the quality of the gamma-ASSR, which is significant in clinical application. The results suggested that 40 Hz ASSR evoked by chirp stimuli had the best performance and was expected to be used in clinical practice, especially in the field of mental diseases such as schizophrenia, Alzheimer’s disease, and affective disorder.

The β-Secretase Enzyme BACE1: A Biochemical Enigma for Alzheimer’s Disease

2020 ◽  
Vol 19 (3) ◽  
pp. 184-194
Author(s):  
Hirak Shah ◽  
Ashish Patel ◽  
Vruti Parikh ◽  
Afzal Nagani ◽  
Bhargav Bhimani ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Precursor Protein ◽  
Small Molecule ◽  
Normal Function ◽  
Precursor Protein ◽  
Voltage Gated ◽  
Small Series ◽  
The Brain ◽  
Translational Level

Beta site amyloid precursor protein cleaving enzyme 1 (BACE1) is a rational target in Alzheimer’s Disease (AD) drug development due to its role in amyloidogenic cleavage of Amyloid Precursor Protein (APP) in generating Amyloid &#946; (A&#946;). This &#946;-secretase cleaves not only Amyloid Precursor Protein (APP) and its homologues, but also small series of substrates including neuregulin and &#946; subunit of voltage-gated sodium channel that play a very important role in the development and normal function of the brain. Moreover, BACE1 is modulated at the post-translational level by several factors that are associated with both physiological and pathological functions. Since the discovery of BACE1 over a decade ago, medicinal chemistry and pharmacokinetics of BACE1 small molecule inhibitors have proven challenging for the treatment of Alzheimer’s disease.

Potentially modifiable factors associated with agitation and aggression in Alzheimer’s disease: results of the ICTUS study

2019 ◽  
Vol 31 (10) ◽  
pp. 1509-1516 ◽  
Author(s):  
Adelaide de Mauleon ◽  
Maria Soto ◽  
Pierre Jean Ousset ◽  
Fati Nourhashemi ◽  
Benoit Lepage ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Affective Disorder ◽  
Positive Impact ◽  
Neuropsychiatric Symptoms ◽  
Cognitive Status ◽  
Community Dwelling ◽  
Factors Associated ◽  
Modifiable Factors ◽  
The Impact

ABSTRACTObjectives:To study potentially modifiable factors associated with the severity of agitation or aggression (A/A) symptoms among Alzheimer’s disease (AD) patients.Design:Data from the Impact of Cholinergic Treatment Use (ICTUS) study, European longitudinal prospective observational study.Setting:Community dwelling outpatients included in 29 European memory clinics.Participants:1375 participants with probable AD (Mini-Mental State Examination score of 10–26) with an informal caregiver.Measurements:At baseline and twice yearly over the two-year follow-up, patients underwent comprehensive clinical and neuropsychological assessments: sociodemographic data, cognitive status, functional impairment, and assessment of neuropsychiatric symptoms based on Neuro-Psychiatric Inventory (NPI). The ZARIT scale assessed the caregiver’s burden. The variable of interest was the severity of the item of A/A of the NPI. To study factors associated to the severity of A/A symptoms six months later, a multivariate mixed regression model was used.Results:Frequency of A/A symptom varied from 30% to 34% at each visit. Two factors were found to be independently associated with the severity of A/A: (1) the presence of affective disorder (anxiety, depression, and/or irritability) that increased the severity of the A/A by 0.89 point (coefficient:0.89; 95% Confidence Interval (CI) = [0.48,1.30], p < 0.001), and (2) a severe caregiver burden that increased the severity of the A/A by 1.08 point (coefficient:1.08; 95% CI = [0.69,1.47], p < 0.001).Conclusion:Research should evaluate whether the identification and treatment of an affective disorder along with the evaluation and optimal management of the caregiver would have a positive impact on the course of A/A in mild to moderate AD patients.

scholarly journals Mis-expression of the Alzheimer’s disease associated gene Ankyrin causes memory loss and shortened lifespan in Drosophila

2018 ◽  
Author(s):  
James P Higham ◽  
Bilal R Malik ◽  
Edgar Buhl ◽  
Jenny Dawson ◽  
Anna S Ogier ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Beta ◽  
Neuronal Excitability ◽  
Therapeutic Potential ◽  
Association Studies ◽  
Treatment Options ◽  
Memory Loss ◽  
Normal Function ◽  
Mutant Proteins

ABSTRACTAlzheimer’s disease (AD) is the most common form of dementia and is characterized by the accumulation of extracellular amyloid beta (Aβ) plaques and intracellular neurofibrillary tangles of hyperphosphorylated Tau, including the 4R0N isoform. Recent epigenome-wide association studies (EWAS) of AD have identified a number of loci that are differentially methylated in AD cortex. Indeed, hypermethylation of the Ankyrin 1 (ANK1) gene in AD has been reported in the cortex in numerous different post-mortem brain cohorts. Little is known about the normal function of ANK1 in the healthy brain, nor the role it may play in AD. We have generated Drosophila models to allow us to functionally characterize Drosophila Ank2, the ortholog of human ANK1. These models have targeted reduction in the expression of Ank2 in neurons. We find that Drosophila with reduced neuronal Ank2 expression have shortened lifespan, reduced locomotion, reduced memory and reduced neuronal excitability similar to flies overexpressing either human mutant APP (that leads to Aβ42 production) and MAPT (that leads to 0N4R Tau). Therefore, we show that the mis-expression of Ank2 can drive disease relevant processes and phenocopy some features of AD and we propose targeting ANK1 may have therapeutic potential. This represents the first study to characterize a gene implicated in AD, which was nominated from EWAS.Author summaryThe majority (>95%) of Alzheimer’s disease (AD) cases are sporadic, with their incidence attributed to common genetic mutations, epigenetic variation, aging and the environment. There is no cure for AD and only limited treatment options which only treat the symptoms of AD and only work in some people. Recent epigenome-wide association studies (EWAS) in AD have highlighted hypermethylation of the Ankyrin1 (ANK1) gene in AD cortex. Little is known of the normal role of the gene in the brain. Here, we have demonstrated that Drosophila with reduced neuronal expression of the Drosophila ortholog of human ANK1 (Ank2), can drive AD relevant processes including locomotor difficulties, memory loss and shortened lifespan similar to expression of human amyloid-Beta or tau mutant proteins. Furthermore, increasing Ank2 expression reversed the memory loss caused by expression of human amyloid-Beta or tau mutant proteins, suggesting that targeting ANK1 may have therapeutic potential. This represents the first study to characterize a gene implicated in AD, which was nominated from EWAS.

scholarly journals Tau Protein Interaction Partners and Their Roles in Alzheimer’s Disease and Other Tauopathies

2021 ◽  
Vol 22 (17) ◽  
pp. 9207 ◽  
Author(s):  
Jakub Sinsky ◽  
Karoline Pichlerova ◽  
Jozef Hanes
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Tau Protein ◽  
Critical Role ◽  
Neuronal Loss ◽  
Paired Helical Filaments ◽  
Normal Function ◽  
Tau Proteins ◽  
Proper Function ◽  
Interaction Partners

Tau protein plays a critical role in the assembly, stabilization, and modulation of microtubules, which are important for the normal function of neurons and the brain. In diseased conditions, several pathological modifications of tau protein manifest. These changes lead to tau protein aggregation and the formation of paired helical filaments (PHF) and neurofibrillary tangles (NFT), which are common hallmarks of Alzheimer’s disease and other tauopathies. The accumulation of PHFs and NFTs results in impairment of physiological functions, apoptosis, and neuronal loss, which is reflected as cognitive impairment, and in the late stages of the disease, leads to death. The causes of this pathological transformation of tau protein haven’t been fully understood yet. In both physiological and pathological conditions, tau interacts with several proteins which maintain their proper function or can participate in their pathological modifications. Interaction partners of tau protein and associated molecular pathways can either initiate and drive the tau pathology or can act neuroprotective, by reducing pathological tau proteins or inflammation. In this review, we focus on the tau as a multifunctional protein and its known interacting partners active in regulations of different processes and the roles of these proteins in Alzheimer’s disease and tauopathies.

scholarly journals Biomarkers to Measure Treatment Effects in Alzheimer's Disease: What Should We Look for?

2011 ◽  
Vol 2011 ◽  
pp. 1-4 ◽  
Author(s):  
Kenneth Rockwood
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Treatment Effects ◽  
Treatment Effectiveness ◽  
Statistical Significance ◽  
Objective Measure ◽  
Dose Dependence ◽  
Biological Plausibility ◽  
Outcomes Measures ◽  
Clinical Profiles

It is often surprisingly difficult to tell whether a treatment for Alzheimer's disease is effective. Biomarkers might offer the potential of a quantifiable objective measure of treatment effectiveness. This paper suggests several criteria by which biomarkers might be evaluated as outcomes measures. These include biological plausibility, statistical significance, dose dependence, convergence across measures, and replicability. If biomarkers can meet these criteria, then, pending regulatory approval, they may have a role in the evaluation of treatment effectiveness in Alzheimer's disease. If not, their usefulness may be in supplementing, but not supplanting, clinical profiles of treatment effects.

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