Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 130.690
Filter
1.
Clin Nucl Med ; 49(8): 754-756, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38967508

ABSTRACT

ABSTRACT: Currently, monoamine oxidase B is recognized as the primary target of 18F-THK5351, although 18F-THK5351 was initially developed to target neurofibrillary tangles (NFTs) in Alzheimer disease. When clinically applying 18F-THK5351 PET to visualize ongoing astrogliosis via estimating monoamine oxidase B levels, a crucial concern is how much degree 18F-THK5351 uptake reflects NFTs in in vivo images. To unravel this concern, a head-to-head comparison between 18F-THK5351 and 18F-MK-6240 (estimating NFT) images in the NFT lesion ideally without accompanying astrogliosis is essential. Here, we present such a case suggesting that 18F-THK5351 uptake may not estimate NFTs in in vivo images.


Subject(s)
Neurofibrillary Tangles , Neurofibrillary Tangles/metabolism , Neurofibrillary Tangles/pathology , Humans , Positron-Emission Tomography , Aminopyridines , Biological Transport , Aged , Male , Female , Alzheimer Disease/diagnostic imaging , Alzheimer Disease/metabolism , Isoquinolines , Quinolines
2.
BMC Public Health ; 24(1): 1769, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38961390

ABSTRACT

BACKGROUND: This study aimed to assess the public knowledge regarding Alzheimer's Disease (AD) in Zhuhai, China, focusing on identifying knowledge gaps and the influence of demographic and health factors. METHODS: A cross-sectional study was conducted in Zhuhai, China, from October to November 2022. A total of 1986 residents from 18 communities were selected employing stratified multi-stage equi-proportional sampling. Questionnaires covering general information and the Alzheimer's Disease Knowledge Scale (ADKS) were investigated face-to-face. Ordinal multiclass logistic regression was applied to assess the relationship between AD awareness and demographic and health characteristics. RESULTS: The average ADKS score was 18.5 (SD = 3.36) in Zhuhai. The lowest awareness rates were observed in the "Symptoms" and "Caregiving" subdomains of ADKS, with rates of 51.01% and 43.78%, respectively. The correct rates for the 30 ADKS questions ranged from 16.62 to 92.6%, showing a bimodal pattern with clusters around 80% and 20%. Women (OR = 1.203, 95% CI: 1.009-1.435), individuals aged 60 years or older (OR = 2.073, 95% CI: 1.467-2.932), those living in urban areas (OR = 1.361, 95% CI: 1.117-1.662), higher average monthly household income per capita (OR = 1.641, 95% CI: 1.297-2.082), and without any neurological or mental disorders (OR = 1.810, 95% CI: 1.323-2.478) were more likely to have higher levels of awareness about Alzheimer's disease. CONCLUSIONS: Adults in Zhuhai show a limited knowledge of AD, particularly in the 'Symptoms' and 'Caregiving' subdomains. Upcoming health campaigns must focus on bridging the knowledge gaps in different subdomains of AD, especially among subgroups with lower awareness, as identified in our study.


Subject(s)
Alzheimer Disease , Health Knowledge, Attitudes, Practice , Humans , Cross-Sectional Studies , China/epidemiology , Male , Female , Middle Aged , Aged , Adult , Surveys and Questionnaires , Young Adult
6.
AAPS PharmSciTech ; 25(6): 149, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38954224

ABSTRACT

Silibinin (SIL) Encapsulated Nanoliquid Crystalline (SIL-NLCs) particles were prepared to study neuroprotective effect against amyloid beta (Aß1-42) neurotoxicity in Balb/c mice model. Theses NLCs were prepared through hot emulsification and probe sonication technique. The pharmacodynamics was investigatigated on Aß1-42 intracerebroventricular (ICV) injected Balb/c mice. The particle size, zeta potential and drug loading were optimized to be 153 ± 2.5 nm, -21 mV, and 8.2%, respectively. Small angle X-ray (SAXS) and electron microscopy revealed to crystalline shape of SIL-NLCs. Thioflavin T (ThT) fluroscence and circular dichroism (CD) technique were employed to understand monomer inhibition effect of SIL-NLCs on Aß1-4. In neurobehavioral studies, SIL-NLCs exhibited enhanced mitigation of memory impairment induced on by Aß1-42 in T-maze and new object recognition test (NORT). Whereas biochemical and histopathological estimation of brain samples showed reduction in level of Aß1-42 aggregate, acetylcholine esterase (ACHE) and reactive oxygen species (ROS). SIL-NLCs treated animal group showed higher protection against Aß1-42 toxicity compared to free SIL and Donopezil (DPZ). Therefore SIL-NLCs promises great prospect in neurodegenerative diseases such as Alzheimer's disease.


Subject(s)
Amyloid beta-Peptides , Mice, Inbred BALB C , Neuroprotective Agents , Peptide Fragments , Silybin , Animals , Amyloid beta-Peptides/toxicity , Amyloid beta-Peptides/metabolism , Mice , Silybin/pharmacology , Silybin/administration & dosage , Peptide Fragments/toxicity , Neuroprotective Agents/pharmacology , Neuroprotective Agents/administration & dosage , Male , Brain/drug effects , Brain/metabolism , Brain/pathology , Particle Size , Nanoparticles/chemistry , Reactive Oxygen Species/metabolism , Disease Models, Animal , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Acetylcholinesterase/metabolism
7.
Sci Rep ; 14(1): 15036, 2024 07 01.
Article in English | MEDLINE | ID: mdl-38951633

ABSTRACT

Overly restrictive clinical trial eligibility criteria can reduce generalizability, slow enrollment, and disproportionately exclude historically underrepresented populations. The eligibility criteria for 196 Alzheimer's Disease and Related Dementias (AD/ADRD) trials funded by the National Institute on Aging were analyzed to identify common criteria and their potential to disproportionately exclude participants by race/ethnicity. The trials were categorized by type (48 Phase I/II pharmacological, 7 Phase III/IV pharmacological, 128 non-pharmacological, 7 diagnostic, and 6 neuropsychiatric) and target population (51 AD/ADRD, 58 Mild Cognitive Impairment, 25 at-risk, and 62 cognitively normal). Eligibility criteria were coded into the following categories: Medical, Neurologic, Psychiatric, and Procedural. A literature search was conducted to describe the prevalence of disparities for eligibility criteria for African Americans/Black (AA/B), Hispanic/Latino (H/L), American Indian/Alaska Native (AI/AN) and Native Hawaiian/Pacific Islander (NH/PI) populations. The trials had a median of 15 criteria. The most frequent criterion were age cutoffs (87% of trials), specified neurologic (65%), and psychiatric disorders (61%). Underrepresented groups could be disproportionately excluded by 16 eligibility categories; 42% of trials specified English-speakers only in their criteria. Most trials (82%) contain poorly operationalized criteria (i.e., criteria not well defined that can have multiple interpretations/means of implementation) and criteria that may reduce racial/ethnic enrollment diversity.


Subject(s)
Alzheimer Disease , Clinical Trials as Topic , Patient Selection , Humans , Alzheimer Disease/epidemiology , Alzheimer Disease/diagnosis , Cognitive Dysfunction/epidemiology , Dementia/epidemiology , Eligibility Determination , Ethnicity , National Institute on Aging (U.S.) , United States/epidemiology , Black or African American , Hispanic or Latino , American Indian or Alaska Native , Native Hawaiian or Other Pacific Islander
8.
JMIR Mhealth Uhealth ; 12: e50186, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38959029

ABSTRACT

BACKGROUND: Lifestyle behaviors including exercise, sleep, diet, stress, mental stimulation, and social interaction significantly impact the likelihood of developing dementia. Mobile health (mHealth) apps have been valuable tools in addressing these lifestyle behaviors for general health and well-being, and there is growing recognition of their potential use for brain health and dementia prevention. Effective apps must be evidence-based and safeguard user data, addressing gaps in the current state of dementia-related mHealth apps. OBJECTIVE: This study aims to describe the scope of available apps for dementia prevention and risk factors, highlighting gaps and suggesting a path forward for future development. METHODS: A systematic search of mobile app stores, peer-reviewed literature, dementia and Alzheimer association websites, and browser searches was conducted from October 19, 2022, to November 2, 2022. A total of 1044 mHealth apps were retrieved. After screening, 152 apps met the inclusion criteria and were coded by paired, independent reviewers using an extraction framework. The framework was adapted from the Silberg scale, other scoping reviews of mHealth apps for similar populations, and background research on modifiable dementia risk factors. Coded elements included evidence-based and expert credibility, app features, lifestyle elements of focus, and privacy and security. RESULTS: Of the 152 apps that met the final selection criteria, 88 (57.9%) addressed modifiable lifestyle behaviors associated with reducing dementia risk. However, many of these apps (59/152, 38.8%) only addressed one lifestyle behavior, with mental stimulation being the most frequently addressed. More than half (84/152, 55.2%) scored 2 points out of 9 on the Silberg scale, with a mean score of 2.4 (SD 1.0) points. Most of the 152 apps did not disclose essential information: 120 (78.9%) did not disclose expert consultation, 125 (82.2%) did not disclose evidence-based information, 146 (96.1%) did not disclose author credentials, and 134 (88.2%) did not disclose their information sources. In addition, 105 (69.2%) apps did not disclose adherence to data privacy and security practices. CONCLUSIONS: There is an opportunity for mHealth apps to support individuals in engaging in behaviors linked to reducing dementia risk. While there is a market for these products, there is a lack of dementia-related apps focused on multiple lifestyle behaviors. Gaps in the rigor of app development regarding evidence base, credibility, and adherence to data privacy and security standards must be addressed. Following established and validated guidelines will be necessary for dementia-related apps to be effective and advance successfully.


Subject(s)
Alzheimer Disease , Dementia , Mobile Applications , Humans , Mobile Applications/standards , Mobile Applications/statistics & numerical data , Mobile Applications/trends , Dementia/psychology , Dementia/therapy , Alzheimer Disease/psychology , Alzheimer Disease/therapy , Telemedicine/standards
9.
Sci Rep ; 14(1): 15436, 2024 07 04.
Article in English | MEDLINE | ID: mdl-38965280

ABSTRACT

Alzheimer disease (AD) is the cause of dementia and accounts for 60-80% cases. Tumor Necrosis Factor-alpha (TNF-α) is a multifunctional cytokine that provides resistance to infections, inflammation, and cancer. It developed as a prospective therapeutic target against multiple autoimmune and inflammatory disorders. Cholinergic insufficiency is linked to Alzheimer's disease, and several cholinesterase inhibitors have been created to treat it, including naturally produced inhibitors, synthetic analogs, and hybrids. In the current study, we tried to prepared compounds may also support the discovery and development of novel therapeutic and preventative drugs for Alzheimer's using manganese tetroxide nanoparticles (Mn3O4-NPs) as a catalyst to generate compounds with excellent reaction conditions. The Biginelli synthesis yields 4-(4-cyanophenyl)-6-oxo-2-thioxohexahydropyrimidine-5-carbonitrile when the 4-cyanobenzaldehyde, ethyl cyanoacetate, and thiourea were coupled with Mn3O4-NPs to produce compound 1. This multi-component method is non-toxic, safe, and environmentally friendly. The new approach reduced the amount of chemicals used and preserved time. Compound 1 underwent reactions with methyl iodide, acrylonitrile, chloroacetone, ethyl chloroacetate, and chloroacetic acid/benzaldehyde, each of the synthetized compounds was docked with TNF-α converting enzyme. These compounds may also support the discovery and development of novel therapeutic and preventative drugs for Alzheimer's disease. The majority of the produced compounds demonstrated pharmacokinetic features, making them potentially attractive therapeutic candidates for Alzheimer's disease treatment.


Subject(s)
Alzheimer Disease , Manganese Compounds , Molecular Docking Simulation , Nanoparticles , Oxides , Pyrimidines , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Pyrimidines/chemistry , Pyrimidines/pharmacology , Pyrimidines/pharmacokinetics , Manganese Compounds/chemistry , Manganese Compounds/pharmacology , Animals , Nanoparticles/chemistry , Oxides/chemistry , Oxides/pharmacology , Humans , Rats , Male
10.
BMC Geriatr ; 24(1): 577, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38965455

ABSTRACT

INTRODUCTION: Knowledge sharing can only happen in the context of a trusting and supportive environment, such as evolves in communities of practice and their virtual equivalent, virtual communities of practice. The main objective of this study was to understand knowledge sharing between participants in a virtual community of practice of caregivers of people with Alzheimer's. METHODS: The authors designed their own mobile application, and two virtual communities of practice were created independently and differentiated by how they were moderated: one by an expert caregiver and the other by three health professionals. 38 caregivers and four moderators were involved in the study, which ran between July 2017 and April 2018. A total of 1925 messages were exchanged within the two communities and used as data in the study. Message data was analysed using LINKS (Leveraging Internet Networks for knowledge sharing). RESULTS: Participants were more motivated to acquire knowledge related to caring for the person with Alzheimer's rather than caring for themselves. The purpose of the messages was to inform others about the sender and not to seek answers. It seems that the interaction was more to socialise and to feel heard, than to gain information. Face to face meetings appear to have accelerated community development. On nearly every parameter, behaviour was significantly different in the two communities, reflecting the importance of the character of the moderator. Caring for oneself was a much stronger theme in the community that included health professionals. Experiential knowledge sharing was particularly strong in the group led by a caregiver. DISCUSSION: Caregivers adapted the virtual community of practice to their own needs and mainly shared social knowledge. This focus on social support, which seems to be more valued by the caregivers than information about the disease, was not an expected pattern. Virtual communities of practice where peers count on each other, function more as a support group, whereas those moderated by health professionals function more as a place to go to acquire information. The level of interactivity points to such communities being important for knowledge sharing not mere knowledge transfer.


Subject(s)
Alzheimer Disease , Caregivers , Information Dissemination , Humans , Caregivers/psychology , Alzheimer Disease/psychology , Male , Information Dissemination/methods , Female , Aged , Middle Aged , Adult , Health Knowledge, Attitudes, Practice
11.
BMC Neurosci ; 25(1): 30, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38965489

ABSTRACT

BACKGROUND: Alzheimer's disease (AD) and frontotemporal dementia (FTD) are the two most common neurodegenerative dementias, presenting with similar clinical features that challenge accurate diagnosis. Despite extensive research, the underlying pathophysiological mechanisms remain unclear, and effective treatments are limited. This study aims to investigate the alterations in brain network connectivity associated with AD and FTD to enhance our understanding of their pathophysiology and establish a scientific foundation for their diagnosis and treatment. METHODS: We analyzed preprocessed electroencephalogram (EEG) data from the OpenNeuro public dataset, comprising 36 patients with AD, 23 patients with FTD, and 29 healthy controls (HC). Participants were in a resting state with eyes closed. We estimated the average functional connectivity using the Phase Lag Index (PLI) for lower frequencies (delta and theta) and the Amplitude Envelope Correlation with leakage correction (AEC-c) for higher frequencies (alpha, beta, and gamma). Graph theory was applied to calculate topological parameters, including mean node degree, clustering coefficient, characteristic path length, global and local efficiency. A permutation test was then utilized to assess changes in brain network connectivity in AD and FTD based on these parameters. RESULTS: Both AD and FTD patients showed increased mean PLI values in the theta frequency band, along with increases in average node degree, clustering coefficient, global efficiency, and local efficiency. Conversely, mean AEC-c values in the alpha frequency band were notably diminished, which was accompanied by decreases average node degree, clustering coefficient, global efficiency, and local efficiency. Furthermore, AD patients in the occipital region showed an increase in theta band node degree and decreased alpha band clustering coefficient and local efficiency, a pattern not observed in FTD. CONCLUSIONS: Our findings reveal distinct abnormalities in the functional network topology and connectivity in AD and FTD, which may contribute to a better understanding of the pathophysiological mechanisms of these diseases. Specifically, patients with AD demonstrated a more widespread change in functional connectivity, while those with FTD retained connectivity in the occipital lobe. These observations could provide valuable insights for developing electrophysiological markers to differentiate between the two diseases.


Subject(s)
Alzheimer Disease , Brain , Electroencephalography , Frontotemporal Dementia , Humans , Frontotemporal Dementia/physiopathology , Alzheimer Disease/physiopathology , Female , Male , Aged , Electroencephalography/methods , Brain/physiopathology , Middle Aged , Nerve Net/physiopathology , Nerve Net/diagnostic imaging , Neural Pathways/physiopathology
12.
J Mol Neurosci ; 74(3): 62, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38958788

ABSTRACT

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease worldwide and has a great socio-economic impact. Modified oxidative lipid metabolism and dysregulated iron homeostasis have been implicated in the pathogenesis of this disorder, but the detailed pathophysiological mechanisms still remain unclear. Apolipoprotein E (APOE) is a lipid-binding protein that occurs in large quantities in human blood plasma, and a polymorphism of the APOE gene locus has been identified as risk factors for AD. The human genome involves three major APOE alleles (APOE2, APOE3, APOE4), which encode for three subtly distinct apolipoprotein E isoforms (APOE2, APOE3, APOE4). The canonic function of these apolipoproteins is lipid transport in blood and brain, but APOE4 allele carriers have a much higher risk for AD. In fact, about 60% of clinically diagnosed AD patients carry at least one APOE4 allele in their genomes. Although the APOE4 protein has been implicated in pathophysiological key processes of AD, such as extracellular beta-amyloid (Aß) aggregation, mitochondrial dysfunction, neuroinflammation, formation of neurofibrillary tangles, modified oxidative lipid metabolism, and ferroptotic cell death, the underlying molecular mechanisms are still not well understood. As for all mammalian cells, iron plays a crucial role in neuronal functions and dysregulation of iron homeostasis has also been implicated in the pathogenesis of AD. Imbalances in iron homeostasis and impairment of the hydroperoxy lipid-reducing capacity induce cellular dysfunction leading to neuronal ferroptosis. In this review, we summarize the current knowledge on APOE4-related oxidative lipid metabolism and the potential role of ferroptosis in the pathogenesis of AD. Pharmacological interference with these processes might offer innovative strategies for therapeutic interventions.


Subject(s)
Alzheimer Disease , Apolipoprotein E4 , Ferroptosis , Lipid Metabolism , Humans , Alzheimer Disease/metabolism , Apolipoprotein E4/metabolism , Apolipoprotein E4/genetics , Animals , Iron/metabolism
13.
Nat Commun ; 15(1): 5540, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38956042

ABSTRACT

Iron plays a fundamental role in multiple brain disorders. However, the genetic underpinnings of brain iron and its implications for these disorders are still lacking. Here, we conduct an exome-wide association analysis of brain iron, measured by quantitative susceptibility mapping technique, across 26 brain regions among 26,789 UK Biobank participants. We find 36 genes linked to brain iron, with 29 not being previously reported, and 16 of them can be replicated in an independent dataset with 3,039 subjects. Many of these genes are involved in iron transport and homeostasis, such as FTH1 and MLX. Several genes, while not previously connected to brain iron, are associated with iron-related brain disorders like Parkinson's (STAB1, KCNA10), Alzheimer's (SHANK1), and depression (GFAP). Mendelian randomization analysis reveals six causal relationships from regional brain iron to brain disorders, such as from the hippocampus to depression and from the substantia nigra to Parkinson's. These insights advance our understanding of the genetic architecture of brain iron and offer potential therapeutic targets for brain disorders.


Subject(s)
Brain , Exome Sequencing , Iron , Humans , Iron/metabolism , Brain/metabolism , Male , Female , Mendelian Randomization Analysis , Genome-Wide Association Study , Parkinson Disease/genetics , Parkinson Disease/metabolism , Middle Aged , Genetic Predisposition to Disease/genetics , Aged , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Adult , Alzheimer Disease/genetics , Alzheimer Disease/metabolism
14.
Nat Commun ; 15(1): 5539, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38956096

ABSTRACT

Blood-based biomarkers of Alzheimer disease (AD) may facilitate testing of historically under-represented groups. The Study of Race to Understand Alzheimer Biomarkers (SORTOUT-AB) is a multi-center longitudinal study to compare AD biomarkers in participants who identify their race as either Black or white. Plasma samples from 324 Black and 1,547 white participants underwent analysis with C2N Diagnostics' PrecivityAD test for Aß42 and Aß40. Compared to white individuals, Black individuals had higher average plasma Aß42/40 levels at baseline, consistent with a lower average level of amyloid pathology. Interestingly, this difference resulted from lower average levels of plasma Aß40 in Black participants. Despite the differences, Black and white individuals had similar longitudinal rates of change in Aß42/40, consistent with a similar rate of amyloid accumulation. Our results agree with multiple recent studies demonstrating a lower prevalence of amyloid pathology in Black individuals, and additionally suggest that amyloid accumulates consistently across both groups.


Subject(s)
Alzheimer Disease , Amyloid beta-Peptides , Biomarkers , Peptide Fragments , White People , Humans , Amyloid beta-Peptides/blood , Male , Female , Alzheimer Disease/blood , Alzheimer Disease/ethnology , Longitudinal Studies , Aged , Peptide Fragments/blood , Biomarkers/blood , Black or African American , Middle Aged , Aged, 80 and over , Black People
15.
J Neuroinflammation ; 21(1): 167, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38956605

ABSTRACT

BACKGROUND: Deposition of amyloid ß, which is produced by amyloidogenic cleavage of APP by ß- and γ-secretase, is one of the primary hallmarks of AD pathology. APP can also be processed by α- and γ-secretase sequentially, to generate sAPPα, which has been shown to be neuroprotective by promoting neurite outgrowth and neuronal survival, etc. METHODS: The global expression profiles of miRNA in blood plasma samples taken from 11 AD patients as well as from 14 age and sex matched cognitively normal volunteers were analyzed using miRNA-seq. Then, overexpressed miR-140 and miR-122 both in vivo and in vitro, and knock-down of the endogenous expression of miR-140 and miR-122 in vitro. Used a combination of techniques, including molecular biology, immunohistochemistry, to detect the impact of miRNAs on AD pathology. RESULTS: In this study, we identified that two miRNAs, miR-140-3p and miR-122-5p, both targeting ADAM10, the main α-secretase in CNS, were upregulated in the blood plasma of AD patients. Overexpression of these two miRNAs in mouse brains induced cognitive decline in wild type C57BL/6J mice as well as exacerbated dyscognition in APP/PS1 mice. Although significant changes in APP and total Aß were not detected, significantly downregulated ADAM10 and its non-amyloidogenic product, sAPPα, were observed in the mouse brains overexpressing miR-140/miR-122. Immunohistology analysis revealed increased neurite dystrophy that correlated with the reduced microglial chemotaxis in the hippocampi of these mice, independent of the other two ADAM10 substrates (neuronal CX3CL1 and microglial TREM2) that were involved in regulating the microglial immunoactivity. Further in vitro analysis demonstrated that both the reduced neuritic outgrowth of mouse embryonic neuronal cells overexpressing miR-140/miR-122 and the reduced Aß phagocytosis in microglia cells co-cultured with HT22 cells overexpressing miR-140/miR-122 could be rescued by overexpressing the specific inhibitory sequence of miR-140/miR-122 TuD as well as by addition of sAPPα, rendering these miRNAs as potential therapeutic targets. CONCLUSIONS: Our results suggested that neuroprotective sAPPα was a key player in the neuropathological progression induced by dysregulated expression of miR-140 and miR-122. Targeting these miRNAs might serve as a promising therapeutic strategy in AD treatment.


Subject(s)
Alzheimer Disease , Chemotaxis , Mice, Inbred C57BL , MicroRNAs , Microglia , MicroRNAs/metabolism , MicroRNAs/genetics , Animals , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Alzheimer Disease/genetics , Mice , Humans , Microglia/metabolism , Microglia/pathology , Male , Chemotaxis/physiology , Female , ADAM10 Protein/metabolism , ADAM10 Protein/genetics , Amyloid Precursor Protein Secretases/metabolism , Amyloid Precursor Protein Secretases/genetics , Mice, Transgenic , Aged , Gene Expression Regulation
16.
Brain Behav ; 14(7): e3611, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38956818

ABSTRACT

PURPOSE: Mild cognitive impairment (MCI) can be the prodromal phase of Alzheimer's disease (AD) where appropriate intervention might prevent or delay conversion to AD. Given this, there has been increasing interest in using magnetic resonance imaging (MRI) and neuropsychological testing to predict conversion from MCI to AD. Recent evidence suggests that the choroid plexus (ChP), neural substrates implicated in brain clearance, undergo volumetric changes in MCI and AD. Whether the ChP is involved in memory changes observed in MCI and can be used to predict conversion from MCI to AD has not been explored. METHOD: The current study used data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database to investigate whether later progression from MCI to AD (progressive MCI [pMCI], n = 115) or stable MCI (sMCI, n = 338) was associated with memory scores using the Rey Auditory Verbal Learning Test (RAVLT) and ChP volumes as calculated from MRI. Classification analyses identifying pMCI or sMCI group membership were performed to compare the predictive ability of the RAVLT and ChP volumes. FINDING: The results indicated a significant difference between pMCI and sMCI groups for right ChP volume, with the pMCI group showing significantly larger right ChP volume (p = .01, 95% confidence interval [-.116, -.015]). A significant linear relationship between the RAVLT scores and right ChP volume was found across all participants, but not for the two groups separately. Classification analyses showed that a combination of left ChP volume and auditory verbal learning scores resulted in the most accurate classification performance, with group membership accurately predicted for 72% of the testing data. CONCLUSION: These results suggest that volumetric ChP changes appear to occur before the onset of AD and might provide value in predicting conversion from MCI to AD.


Subject(s)
Alzheimer Disease , Choroid Plexus , Cognitive Dysfunction , Disease Progression , Magnetic Resonance Imaging , Verbal Learning , Humans , Alzheimer Disease/diagnostic imaging , Alzheimer Disease/physiopathology , Cognitive Dysfunction/diagnostic imaging , Cognitive Dysfunction/physiopathology , Cognitive Dysfunction/diagnosis , Male , Female , Aged , Verbal Learning/physiology , Choroid Plexus/diagnostic imaging , Choroid Plexus/pathology , Aged, 80 and over , Neuropsychological Tests
17.
Sci Rep ; 14(1): 15583, 2024 Jul 06.
Article in English | MEDLINE | ID: mdl-38971870

ABSTRACT

Alzheimer's Disease and Related Dementias (ADRD) affect millions of people worldwide, with mortality rates influenced by several risk factors and exhibiting significant heterogeneity across geographical regions. This study aimed to investigate the impact of risk factors on global ADRD mortality patterns from 1990 to 2021, utilizing clustering and modeling techniques. Data on ADRD mortality rates, cardiovascular disease, and diabetes prevalence were obtained for 204 countries from the GBD platform. Additional variables such as HDI, life expectancy, alcohol consumption, and tobacco use prevalence were sourced from the UNDP and WHO. All the data were extracted for men, women, and the overall population. Longitudinal k-means clustering and generalized estimating equations were applied for data analysis. The findings revealed that cardiovascular disease had significant positive effects of 1.84, 3.94, and 4.70 on men, women, and the overall ADRD mortality rates, respectively. Tobacco showed positive effects of 0.92, 0.13, and 0.39, while alcohol consumption had negative effects of - 0.59, - 9.92, and - 2.32, on men, women, and the overall ADRD mortality rates, respectively. The countries were classified into five distinct subgroups. Overall, cardiovascular disease and tobacco use were associated with increased ADRD mortality rates, while moderate alcohol consumption exhibited a protective effect. Notably, tobacco use showed a protective effect in cluster A, as did alcohol consumption in cluster B. The effects of risk factors on ADRD mortality rates varied among the clusters, highlighting the need for further investigation into the underlying causal factors.


Subject(s)
Alcohol Drinking , Alzheimer Disease , Dementia , Humans , Alzheimer Disease/mortality , Alzheimer Disease/epidemiology , Risk Factors , Male , Female , Dementia/mortality , Dementia/epidemiology , Alcohol Drinking/adverse effects , Alcohol Drinking/epidemiology , Global Health , Cardiovascular Diseases/mortality , Cardiovascular Diseases/epidemiology , Prevalence , Tobacco Use/adverse effects , Tobacco Use/epidemiology , Diabetes Mellitus/mortality , Diabetes Mellitus/epidemiology , Life Expectancy , Aged , Cluster Analysis
18.
Genome Biol ; 25(1): 179, 2024 Jul 07.
Article in English | MEDLINE | ID: mdl-38972974

ABSTRACT

Pathogenic allele silencing is a promising treatment for genetic hereditary diseases. Here, we develop an RNA-cleaving tool, TaqTth-hpRNA, consisting of a small, chimeric TaqTth, and a hairpin RNA guiding probe. With a minimal flanking sequence-motif requirement, in vitro and in vivo studies show TaqTth-hpRNA cleaves RNA efficiently and specifically. In an Alzheimer's disease model, we demonstrate silencing of mutant APPswe mRNA without altering the wild-type APP mRNA. Notably, due to the compact size of TaqTth, we are able to combine with APOE2 overexpression in a single AAV vector, which results in stronger inhibition of pathologies.


Subject(s)
Alzheimer Disease , Gene Silencing , RNA, Messenger , RNA, Messenger/genetics , RNA, Messenger/metabolism , Humans , Alzheimer Disease/genetics , Alzheimer Disease/metabolism , Animals , Mice , Amyloid beta-Protein Precursor/genetics , Amyloid beta-Protein Precursor/metabolism , RNA Cleavage , Genetic Vectors , Dependovirus/genetics
19.
JMIR Aging ; 7: e51520, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38981112

ABSTRACT

BACKGROUND: Social media may be a useful method for research centers to deliver health messages, increase their visibility in the local community, and recruit study participants. Sharing examples of social media-based community outreach and educational programs, and evaluating their outcomes in this setting, is important for understanding whether these efforts have a measurable impact. OBJECTIVE: The aim of this study is to describe one center's social media activities for community education on topics related to aging, memory loss, and Alzheimer disease and related dementias, and provide metrics related to recruitment into clinical research studies. METHODS: Several social media platforms were used, including Facebook, X (formerly Twitter), and YouTube. Objective assessments quantified monthly, based on each platform's native dashboard, included the number of followers, number of posts, post reach and engagement, post impressions, and video views. The number of participants volunteering for research during this period was additionally tracked using a secure database. Educational material posted to social media most frequently included content developed by center staff, content from partner organizations, and news articles or resources featuring center researchers. Multiple educational programs were developed, including social media series, web-based talks, Twitter chats, and webinars. In more recent years, Facebook content was occasionally boosted to increase visibility in the local geographical region. RESULTS: Up to 4 years of page metrics demonstrated continuing growth in reaching social media audiences, as indicated by increases over time in the numbers of likes or followers on Facebook and X/Twitter and views of YouTube videos (growth trajectories). While Facebook reach and X/Twitter impression rates were reasonable, Facebook engagement rates were more modest. Months that included boosted Facebook posts resulted in a greater change in page followers and page likes, and higher reach and engagement rates (all P≤.002). Recruitment of participants into center-affiliated research studies increased during this time frame, particularly in response to boosted Facebook posts. CONCLUSIONS: These data demonstrate that social media activities can provide meaningful community educational opportunities focused on Alzheimer disease and related dementias and have a measurable impact on the recruitment of participants into research studies. Additionally, this study highlights the importance of tracking outreach program outcomes for evaluating return on investment.


Subject(s)
Alzheimer Disease , Social Media , Humans , Longitudinal Studies , Community-Institutional Relations , Patient Selection , Aging/psychology , Aging/physiology , Female , Dementia , Male , Aged
20.
Biochemistry (Mosc) ; 89(6): 1031-1044, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38981699

ABSTRACT

Alzheimer's disease (AD) is a severe neurodegenerative condition affecting millions worldwide. Prevalence of AD correlates with increased life expectancy and aging population in the developed countries. Considering that AD is a multifactorial disease involving various pathological processes such as synaptic dysfunction, neuroinflammation, oxidative stress, and improper protein folding, a comprehensive approach targeting multiple pathways may prove effective in slowing the disease progression. Cellular therapy and its further development in the form of cell vesicle and particularly mitochondrial transplantation represent promising approaches for treating neurodegeneration. The use of synaptosomes, due to uniqueness of their contents, could mark a new stage in the development of comprehensive therapies for neurodegenerative diseases, particularly AD. Synaptosomes contain unique memory mitochondria, which differ not only in size but also in functionality compared to the mitochondria in the neuronal soma. These synaptosomal mitochondria actively participate in cellular communication and signal transmission within synapses. Synaptosomes also contain other elements such as their own protein synthesis machinery, synaptic vesicles with neurotransmitters, synaptic adhesion molecules, and microRNAs - all crucial for synaptic transmission and, consequently, cognitive processes. Complex molecular ensemble ensures maintenance of the synaptic autonomy of mitochondria. Additionally, synaptosomes, with their affinity for neurons, can serve as an optimal platform for targeted drug delivery to nerve cells. This review discusses unique composition of synaptosomes, their capabilities and advantages, as well as limitations of their suggested use as therapeutic agents for treating neurodegenerative pathologies, particularly AD.


Subject(s)
Alzheimer Disease , Synaptosomes , Alzheimer Disease/metabolism , Alzheimer Disease/therapy , Alzheimer Disease/pathology , Humans , Synaptosomes/metabolism , Animals , Mitochondria/metabolism , Synaptic Transmission , Neurons/metabolism , Synapses/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL
...