Journal of Alzheimer's disease reports最新文献

Beta-site amyloid precursor protein cleaving enzyme 2 (BACE2) is one of the most downregulated genes in the brain capillary endothelial cells derived from patients with Alzheimer's disease (AD). Endothelin-1 (ET-1) significantly contributes to the pathogenesis of AD. We hypothesized that loss of BACE2 increases production of ET-1 from human brain microvascular endothelial cells (BMECs). Genetic inactivation of BACE2 in cultured human BMECs significantly upregulated expression and release of ET-1. Mechanistic studies indicated that γ-aminobutyric acid type B receptor subunit 2/transforming growth factor beta 2 signaling pathway mediated the effect of BACE2 inhibition on ET-1 production.

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder marked by memory loss and cognitive decline. Animal models play a key role in exploring its pathophysiological mechanisms.

Objective: To analyze global research trends and knowledge structure in AD pathophysiological mechanisms based on animal models.

Methods: Publications from 2014 to 2023 were retrieved from the Web of Science Core Collection. CiteSpace and VOSviewer were used for bibliometric analysis and data visualization.

Results: A total of 2169 publications were identified, with a steady growth trend. The United States and China were the leading contributors, with Harvard University as a major collaborative hub. The Journal of Alzheimer's Disease published the most articles, while the Journal of Neuroscience had the highest co-citation frequency. Holtzman DM was a key author in the field. Nine keyword clusters were identified, including insulin resistance, amyloid beta, and oxidative stress. Emerging topics include synapse loss, gut microbiota, and NLRP3 inflammasome.

Conclusions: This study provides a concise overview of global research on AD pathophysiological mechanisms in animal models, offering valuable insights for future research directions.

Background: Emerging evidence highlights the potential role of environmental factors, particularly air pollution, in the development and progression of Alzheimer's disease (AD). Air pollutants may contribute to neurodegenerative processes through mechanisms such as oxidative stress, neuroinflammation, and disruption of the blood-brain barrier.

Objective: This review aims to systematically evaluate global cohort studies investigating the association between long-term exposure to key air pollutants-specifically particulate matter (PM2.5), nitrogen dioxide (NO₂), and ozone (O₃)-and the risk of AD.

Methods: A total of 31 peer-reviewed cohort studies were included based on a structured search strategy. We analyzed epidemiological outcomes, exposure assessment methodologies, and geographic trends. Additionally, a bibliometric analysis was conducted using VOSviewer to identify major contributors and emerging research themes.

Results: Findings indicate a consistent association between PM2.5 exposure and increased risk of AD, independent of genetic predisposition and lifestyle factors. Proposed biological mechanisms include oxidative stress, microglial activation, blood-brain barrier disruption, and amyloid-β accumulation. Bibliometric mapping revealed regional concentration of research in North America, Europe, and East Asia, with increasing global interest over the past decade.

Conclusions: There is mounting evidence linking air pollution to Alzheimer's disease. Advances in exposure assessment have improved the accuracy of epidemiological findings. Public health policies targeting air quality control and further studies on molecular and early-life exposures are essential to mitigate the neurotoxic effects of environmental pollutants.

Background: High-fat diet (HFD) consumption is linked to Alzheimer's disease (AD). Identifying changes in the mRNA expression due to the ingestion of HFD in the intestine-often called the second brain due to its dense enteric neurons-could offer insights into AD development and progression.

Objective: This study assesses whether the introduction of HFD at adult-age influence expression of AD-related genes in the intestines of Wild-type (WT) or the amyloid precursor protein/presenilin1 (APP/PS1)-overexpressing Transgenic (TG) rats.

Methods: Twelve-month-old WT and TG rats (male and female) were fed a control diet (CD; 8% energy from fat), or HFD (45% energy from fat) for six months. Ileal tissues were assessed for the mRNA expression of genes responsible for development/progression of AD.

Results: The WT HFD-fed rats (compared to CD-fed rats) showed increased mRNA expression of genes involved in the development of AD. In contrast, the TG HFD-fed female group, showed a higher number of upregulated genes compared to their respective CD-fed TG group. In TG HFD-fed rats there was higher mRNA expression of genes crucial for synaptic transmission such as Brain-derived neurotrophic factor in females and Choline acetyltransferase in males. Expression of Plasminogen was higher in HFD-fed TG female rats and HFD-fed WT male rats. Overall, the HFD-fed WT male showed mRNA expression of genes involved in the development of AD. However, HFD-fed TG females were more vulnerable for the progression of AD. It is likely that the enteric Plasminogen plays a major role in gut-brain axis for the development of AD in WT male, and progression of AD in TG female during the consumption of HFD.

Conclusions: The consumption of HFD perturbed the expression of enteric genes known to be involved in amyloid-β generation, clearance, and degradation, in a sex-dependent manner.

Alzheimer's disease (AD) is a neurodegenerative condition manifesting as cognitive decline, memory deterioration, and behavioral alterations. Late-onset AD accounts for most diagnosed cases, with the onset of symptoms usually occurring after 65 years. At present, there are no proven treatments that alter the course of AD. For early detection and intervention, it is crucial to understand the underlying mechanisms and identify promising biomarkers for AD. Research suggests that the pathological processes of AD initiate years before the emergence of noticeable symptoms, which makes the early diagnosis more challenging. While various biomarkers, such as cognitive tests, imaging, and biological markers in blood and cerebrospinal fluid, have been proposed for early detection, their reliability, as matched with symptomatic stages, varies significantly. As a component of the central nervous system, the retina has attracted attention as a potential site for studying AD-related changes. Studies from human and animal models have revealed structural, vascular, functional, and metabolic changes in the retina through the early phases of AD. Furthermore, advances in ophthalmic technologies have facilitated the identification and characterization of AD-related changes such as amyloid-β and tau-protein deposition. This review provides an overview and perspective on AD as they relate to the retina and highlights the importance of ocular changes as surrogates for understanding and diagnosing AD.

Background: Better cognitive tools to predict disease progression in mild cognitive impairment (MCI) and Alzheimer's disease (AD) are needed.

Objective: In this prospective longitudinal cohort, we are testing if changes in the cognitive domains of executive functioning and processing speed can predict global cognitive decline.

Methods: We assessed patients with MCI, AD, and cognitively healthy controls (cHC) using NIH toolbox assessments for processing speed and executive functioning and overall cognitive decline by the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog).

Results: Among 184 participants over a median follow-up of 540 days, both between- and within-subjects variance in NIH toolbox and ADAS-Cog assessments increased from cHC to MCI to AD patients. Among patients with AD (n = 24), pattern comparison processing speed (PCPS) and dimensional change card sort tests (DCCS) declined at 3 and 6 months prior to global cognitive decline (p = 0.008 and 0.0012). A 5-point decrease in either PCPS or DCCS increased risk of global cognitive decline (HR 1.32 (1.08-1.60) and 1.62 (1.16-2.26)).

Conclusions: Testing for cognitive domains of processing speed and executive functioning may predict subsequent global cognitive.

Background: Dementia, mainly caused by Alzheimer's disease (AD), is a leading cause of mortality and disability in the elderly. However, inconsistencies in diagnostic and inclusion criteria challenge the design and comparability of AD clinical trials.

Objective: To review recent AD clinical trials, focusing on diagnostic methods and inclusion criteria, and identify trends and gaps to inform future research.

Methods: We systematically searched Web of Science, PubMed, and Google Scholar for AD clinical trials, extracting data on diagnostic criteria, disease stage, cognitive assessments, biomarker use, and participant age.

Results: Of the 27,471 articles screened, 71 studies were included in the final review. Most were conducted in North America (52%) and Europe (34%). NINCDS-ADRDA (56%) and NIA-AA 2011 (30%) were the most used diagnostic criterion, with the latter increasingly adopted in recent years. Over half focused on mild-to-moderate AD (56%), 16% on mild AD, and 13% included mild cognitive impairment/mild AD populations, with growing interest in early-stage interventions. However, only a minority reported notable cognitive improvements. The Mini-Mental State Examination was the most frequently used assessment tool (86%), though 36 different cutoff schemes were identified. Biomarkers were used in 38% of studies, mainly in the past three years, while others relied on symptom-based or imaging approaches. Participants ranged from 45 to 95 years old, with 50 as the most common lower age limit.

Conclusions: Symptom-based criteria still dominate AD trials. Given the limited efficacy of single interventions, future studies should consider multimodal, non-invasive approaches and prioritize objective biomarkers to enhance consistency and diagnostic precision.

Background: The Research Attitudes Questionnaire (RAQ), developed to predict individuals' willingness to participate, is often used in Alzheimer's Disease and related dementia research.

Objective: The present investigation aimed to examine the suitability of the RAQ across age groups and three different racialized identities, i.e., to see whether the RAQ showed measurement invariance.

Methods: We administered the RAQ to six groups of participants: 457 younger and 594 older African Americans, 207 younger and 339 older American Indian/Alaska Native, and 173 younger and 679 older non-Hispanic White adults.

Results: Confirmatory factor analysis indicated that the best-fitting model was one-factor. All six groups fit the model well, with Comparative Fit Indices > 0.95. A series of cross-sample invariance tests using increasing constraints on factor loadings, means, and residuals revealed evidence of configural invariance, metric invariance, and partial scalar invariance.

Conclusions: These findings support the suitability of the RAQ for cross-cultural and/or age comparisons of willingness to engage in research in the groups and context studied.

Background: Because music-based interventions (MBIs) are not standard of care for Alzheimer's disease and Alzheimer's disease related dementias (AD/ADRD), it is likely that the application of them in different care communities differs widely. Additionally, there is no standardized use of personalized music listening and group music activities.

Objective: The purpose of this pilot study was to assess the current use of music in long-term care communities, to identify trends and patterns of music use and record the perceived benefits that music use provides.

Methods: This study utilized a qualitative research approach using semi-structured interviews with care community staff and care community observations to examine the role that music played as a therapeutic tool for individuals with AD/ADRD living in care communities.

Results: Of the five communities visited, interviews were conducted at four communities. Two staff members were interviewed at each participating community resulting in eight total interviews. Both live and recorded music was used actively and passively and was perceived to stimulate memory, increase engagement, and energize or calm as needed.

Conclusions: Elder care community staff are finding ways to integrate music because they believe it to be helpful. The adaptability of music for use in many situations is makes it useful throughout most of the day across a wide range staff duties and resident needs. The evidence for benefit of MBIs is growing, however, further investigation into MBI's in this setting is needed to develop guidelines for best practices incorporating music into elder care for people with dementia.

Background: Accumulating evidence implicates infectious pathogens as triggers of immune-inflammatory processes that contribute to neurodegeneration. Inflammation in both the brain and peripheral circulation is recognized as a critical factor in the development and progression of cognitive decline and neurodegenerative disorders, including Alzheimer's disease.

Objective: This retrospective case-control study investigated the association between cognitive impairment and presence of serum antibodies to seven pathogens in older adults.

Methods: One hundred sixty-five participants aged ≥ 65 years from the Panama Aging Research Initiative Health Disparities (PARI-HD) study were evaluated. Presence of IgG antibodies against Toxoplasma gondii, Herpes Simplex Virus Type 1 (HSV-1), Human Cytomegalovirus (HCMV), Helicobacter pylori, Chlamydia pneumoniae, Treponema pallidum, and Trypanosoma cruzi was measured. Participant demographics, inflammatory biomarkers and cognitive-functional factors were analyzed for associations with single/multiple pathogen-specific antibodies reactivity using multivariable regression models.

Results: Only C. pneumoniae seropositivity was significantly different between cognitively unimpaired and impaired groups (p = 0.02) and increasing TNF-α levels were directly associated with C. pneumoniae seropositivity (OR = 2.08, CI_95% 1.0-4.1, p = 0.04). Additionally, cumulative exposure to infectious agents increased the likelihood of cognitive impairment (OR = 1.51, CI_95% 1.01-2.26, p = 0.04) and was associated with slower processing speed as measured by TMT A test (OR = 17.43, CI_95% 2.32-32.53, p = 0.02). Notably, the presence of C. pneumoniae in multiple pathogen interactions further raised the likelihood of cognitive impairment (OR = 4.07, CI_95% 1.24-13.36, p = 0.03).

Conclusions: These results enhance our understanding of cognitive impairment in a Hispanic population and underscore the need for further studies on the role of C. pneumoniae and multi-pathogen infection in Alzheimer's disease.