BackgroundAlzheimer's disease is the leading cause of dementia and constitutes a major public health problem. Recent research suggests that certain chronic infections, particularly periodontal infections, may play a role in the development or progression of this disease. Among the bacteria involved in periodontal disease, Porphyromonas gingivalis has attracted particular attention from researchers.ObjectiveIn this way, the aim of this thesis, conducted in the form of a scoping review, was to analyze existing scientific data on the relationship between Porphyromonas gingivalis infection and Alzheimer's disease.MethodsTo achieve this, a literature search was conducted in several scientific databases leading to the selection of fourteen studies that met the inclusion criteria.ResultsSome of the selected studies have shown the presence of Porphyromonas gingivalis or its virulence factors in the brain tissues of patients with Alzheimer's disease. Experimental studies also indicate that this bacterium can promote certain mechanisms involved in neurodegeneration, namely inflammation and accumulation of amyloid-β.ConclusionsSelected studies point to the existence of an association between exposure to periodontal bacteria and an increased risk of developing Alzheimer's disease.
BackgroundPeople living with Alzheimer's disease often require support from their relatives, who may face emotional and physical challenges in their role. Up to 90% of people living with cognitive impairment experience unmet needs such as wandering.ObjectiveThe aim of the study was to analyze the narrative of relatives of people living with Alzheimer's disease experiencing unsatisfied behavioral needs and whether this has a relationship with levels of burden.MethodsRelatives who cared for a family member with Alzheimer's disease at home participated in a structured interview with a psychologist and completed the Zarit Burden Interview to assess caregiver burden. An analysis was conducted of the frequency of words used in the relatives' responses to the question "What is your experience of your loved one's wandering?".ResultsA total of 15 relatives participated in the study. Relatives with higher levels of burden related to their role as caregivers were more likely to use words such as "disorder" (on average once per interview), "problem" (on average three times per interview), and "difficulty" (on average twice per interview), than people with low levels of burden. For people with low levels of burden, the word "need" appeared as a significant expression (on average four times per interview).ConclusionsRelatives who experience less burden are more likely to understand the reasons behind their loved ones' need or desire to wander. They are less likely to perceive this behavior as a problem and restrict the person's freedom of movement for their own safety.
BackgroundAlzheimer's disease (AD) is a neurodegenerative disorder whose incidence grows with age and its development is gradual. However, if detected earlier there is much hope to prevent further exacerbation. In this study, NGS transcriptomics data from cases and controls with Braak scores of III-IV were investigated that all possessed neurofibrillary tangles (NFTs) in their fusiform gyrus.ObjectiveThe aim of this study was to discover the underlying mechanisms at gene level which could explain cognitive impairment by considering the presence of NFTs in both groups.MethodsDifferentially expressed genes (DEGs) were determined and ROC AUC were evaluated by leave-one-out cross-validation method on the diagnostic DEGs to detect candidate gene biomarkers. WGCNA was employed to identify co-expression modules with their trait association. Finally, in silico hybridization of lncRNAs from potential biomarkers with important AD-related microRNAs was carried out.ResultsHighly ranked potential diagnostic gene biomarkers revealed assessed AUC ranges of 80-90% in which RASGRF2-AS1 demonstrated the highest value. WGCNA demonstrated upregulated genes in favor of dephosphorylation of tau, proper proteostasis and vascular health in resilient controls whereas dysfunctional proteostasis, chronic protein misfolding, heightened cellular stress and tetrahydrobiopterin deficiency were attributed to cognitive impairment in AD patients. In silico analyses predicted some lncRNAs with a high possibility of acting as sponge for AD-related microRNAs.ConclusionsThis study discovered potential diagnostic gene biomarkers and transcriptional signatures that could explain the mechanisms of cognitive decline by considering the existence of NFTs, which could provide further insight for diagnosis and treatment of the disease.
BackgroundAlzheimer's disease (AD) is the most common cause of dementia whose prevalence is projected to increase significantly in the coming decades. The recent advent of disease modifying therapies is a welcome development; however, it is also now apparent that early treatment maximizes the benefits of these drugs. Therefore, it is important to develop reliable methods of disease detection, preferably from an easily accessible matrix such as blood.ObjectiveTo develop a method for detecting AD from circulating white blood cells using spectral confocal microscopy.MethodsUsing K114-stained wild type and 5xFAD transgenic mouse cortical sections as proof-of-principle, spectral imaging of K114 fluorescence coupled with a signal processing/machine learning pipeline (spectral wavelet decomposition, dimensionality reduction, support vector machine classifier) can reliably distinguish non-plaque background parenchyma in the two strains. We then performed immunoprecipitation of Aβ from peripheral blood mononuclear cells (PBMCs) obtained from non-neurological controls and histopathologically-proven AD cases. We spectrally imaged the immunobeads labeled with K114, then used similar machine learning methods to classify control versus AD samples.ResultsNormal-appearing non-plaque 5xFAD background was reliably distinguished from wild type mouse brain. We could also classify AD with a high degree of reliability (area under the receiver operating curve = 0.95, p = 6.1e-5) and predict neuropathological scores from these blood elements (R = 0.89).ConclusionsOur spectral imaging method, together with automated machine learning analysis of spectral micrographs, using readily obtainable PBMCs from blood, represents a potentially useful approach for detection of AD in living subjects.
BackgroundAlthough studies have explored tea and coffee in relation to Alzheimer's disease, no century-scale analysis has jointly examined both within a unified primary-evidence framework.ObjectiveThis study maps the structural, thematic, and temporal evolution of coffee and tea research in cognitive aging.MethodsScopus-indexed original English articles (1911-2025) were retrieved using a structured Boolean strategy under PRISMA guidance. Analyses were conducted using Bibliometrix and VOSviewer. Performance metrics, collaboration networks, co-citation mapping, Bradford's Law, co-word clustering, thematic evolution, and overlay visualization were applied to full-period and recent (2021-2025) datasets.ResultsA total of 2873 articles across 1285 sources demonstrated steady annual growth (4.96%) and substantial citation impact (mean 40.17 citations per document). Research productivity was concentrated in high-income countries, led by the United States, United Kingdom, and China, reflecting core-periphery stratification and citation asymmetry. Collaboration networks showed hub dominance with dense transatlantic-Eurasian linkages. Bradford analysis identified a limited core of highly productive journals. Thematic evolution revealed persistent anchoring in Alzheimer's disease, oxidative stress, and neuroprotection, with sustained prominence of coffee, caffeine, tea, and polyphenols. Recent years indicate translational expansion integrating microbiome science and computational methods. Overlay visualization demonstrated temporal stratification, highlighting emerging themes such as gut microbiota and deep learning alongside stable beverage-related cognitive frameworks.ConclusionsCoffee and tea research in cognitive aging has evolved into a mature, mechanistically grounded, and globally stratified field, increasingly integrating translational, microbiome, and computational approaches in dementia-related investigations.
BackgroundVarious studies have reported altered expression of metalloproteinases in Alzheimer's disease (AD); however, expression profiles of each metalloproteinase during cognitive decline have not yet been fully characterized.ObjectiveThe purpose of this systematic review was to generate a comprehensive overview of metalloproteinases and their cognate inhibitors expression in AD and mild cognitive impairment (MCI), across sample matrices, to determine whether metalloproteinases are dysregulated in AD and may have predictive power in individuals with cognitive decline.MethodsAn electronic literature search was conducted in PubMed, EMBASE, Scopus and MEDLINE from inception to December 2024. Sixty-one publications reporting metalloproteinase and inhibitor levels in 8576 patients with AD or MCI, and 7333 controls were included in the systematic review, twenty-one of which were extracted for meta-analysis. Standardized mean difference (SMD) was used to illustrate comparisons, and the Newcastle-Ottawa scale to assess bias.ResultsHigher levels of cerebrospinal fluid (CSF) tissue inhibitor of metalloproteinase-2 (TIMP-2; p = 0.0003) were observed in the AD group and in patients with MCI (p = 0.0009) compared to cognitively healthy controls. Following sensitivity analysis, significantly higher levels of CSF MMP-10 (p = 0.0005) and lower plasma TIMP-2 (p = 0.004) were also noted in patients with AD. TIMP-3, across all sample matrices, was decreased in patients with MCI versus controls (p = 0.01).ConclusionsSignificantly altered levels of metalloproteinases and their inhibitors were verified between patients with AD and MCI, representing potential biomarkers and prospective therapeutic targets for cognitive decline. This study was registered with PROSPERO, CRD42024628202.
BackgroundLanguage and communication disorders in dementia with Lewy bodies (DLB) remain understudied and have rarely been explored from the caregiver's perspective. Comparative studies with Alzheimer's disease (AD) are also limited.ObjectiveTo provide an initial overview of language and communication profiles in DLB, compared to AD and healthy elderly controls (HC); to assess subjective complaints reported by patients, caregivers and healthcare professionals; and to explore their relationships with rapid language screening. A further aim was to aid non-specialist professionals in identifying patients needing speech therapy referral.MethodsSeventeen DLB patients, 15 AD patients, and 11 HC completed the Diagnostic Tool for Language Assessment and the alpha version of the Communication Support Needs Assessment Tool for Dementia (CoSNAT-D), alongside a semi-directed interview (SDI). Proxy-ratings were also collected from caregivers and healthcare professionals (HP) for the CoSNAT-D and SDI.ResultsCompared to HC, DLB patients showed significantly poorer performance in repetition, verbal working memory, sentence comprehension and dictation, and reported more communication difficulties. Compared to AD patients, DLB patients had greater impairments in phonemic fluency, and more frequent reports of discomfort, vocal changes, and difficulties with writing and handwriting execution. Perceptions of communicative difficulties and their functional impact varied across patients, caregivers, and HP.ConclusionsThis study has identified distinct language and communication deficits in DLB versus AD and HC. Discrepancies between patient and caregiver perceptions were frequent in both groups and may contribute to increased caregiver burden. Findings highlight the potential value of rapid screening tools to better support patients and their caregivers.
BackgroundCerebrovascular dysfunction can contribute to the pathophysiology of Alzheimer's disease (AD) and trigger angiogenesis. To date, no prior systematic review and meta-analysis (SRMA) study has attempted to qualitatively and quantitatively review existing literature examining angiogenic factors in AD.ObjectiveIn this review, we aimed to identify markers of angiogenesis in biofluids that can differentiate between individuals with AD and healthy older adults, and inform the role of angiogenesis in AD.MethodsUsing Medline (1946 to August 4, 2021), the literature was systematically searched for articles according to PRISMA guidelines. Angiogenesis and AD terms were searched as keywords and mapped to MeSH headings. A total of 18 studies (including 28 dependent effect sizes) were included in the meta-analysis. Hedges' g was selected as the effect size of interest.ResultsA random-effects model including all eligible biofluid studies revealed a small and nonsignificant overall effect size (combined Hedges' g = -0.26, 95% CI [-1.45, 0.92], p = 0.647), with significant heterogeneity (I2 = 98.6%, p < 0.0001). Moderator analysis revealed no significant difference based on which specific angiogenic biomarker was examined (i.e., vascular endothelial growth factor (VEGF) versus others).ConclusionsVEGF-related marker levels were not significantly different in AD and normal aging. Based on our findings, few studies have examined fibroblast growth factor and platelet-derived growth factor-related markers; however, we believe they warrant further investigation. Identifying novel angiogenic biomarkers could elucidate the role of vascular mechanisms in AD and reveal potential therapeutic targets.
BackgroundBiomarker detection is crucial for diagnosing Alzheimer's disease (AD). A highly promising approach combines non-invasive fundus imaging of the retinal nerve fiber layer (RNFL) with plasma biomarkers. Combining RNFL with plasma neurofilament light chain (pNFL) and phosphorylated Tau181 (P-tau181) may play a significant role in the diagnosis and monitoring of mild cognitive impairment (MCI) and AD.ObjectiveThis study aimed to evaluate the utility of combining RNFL thickness with plasma pNFL and P-tau181 levels for assessing the risk of clinically diagnosed AD.MethodsA total of 143 patients with AD and MCI underwent clinical and cognitive assessments as well as biomarker evaluations (plasma pNFL, P-tau181, RNFL), and receiver operating characteristic (ROC) analysis was finally employed to assess their diagnostic efficacy for clinically diagnosed AD.ResultsSignificant inverse correlations were found between Mini-Mental State Examination scores and pNFL (R2 = 0.344, p < 0.001) and P-tau181 (R2=0.424, p < 0.001). Temporal RNFL thickness was significantly lower in the MCI group versus healthy control (HCs), while the AD group showed intermediate thickness not significantly different from HCs. For AD diagnosis, pNFL achieved the highest area under the curve (AUC=0.748). Combining pNFL with P-tau181 improved the AUC to 0.784, and models further incorporating Apolipoprotein E (APOE) ε4 or RNFL thickness similarly showed high accuracy (AUCs=0.785/0.782).ConclusionsElevated levels of pNFL and P-tau181 are independent risk factors for cognitive decline. Combination with fundus examination confers significant diagnostic utility for clinically diagnosed AD.
BackgroundAlzheimer's disease (AD) is a progressive neurodegenerative disorder whose global prevalence continues to rise, yet treatment options are still limited. Natural medicines, with their potential for multi-target intervention, have become a key direction in AD drug development. However, a systematic overview of research trends in this field based on bibliometric methods is currently lacking.ObjectiveThis study aims to summarize research progress on natural medicines for AD treatment using bibliometric analysis and to identify future research hotspots and trends.MethodsRelevant publications were retrieved from the Web of Science Core Collection. Data visualization and analysis were conducted using VOSviewer, CiteSpace, and R.ResultsA total of 3800 publications were included, involving contributions from 108 countries/regions, 4024 institutions, 18,729 authors, and 706 journals. Publication output showed steady growth, with China and India as the leading contributing countries. Institutions such as the Chinese Academy of Sciences and Kyung Hee University demonstrated high productivity and influence. The research focus has shifted from initial clinical pharmacology and molecular pathology to exploring multi-target mechanisms of natural medicines through network pharmacology and molecular docking. Promising natural agents include Ginkgo biloba, ginseng, curcumin, resveratrol, and Centella asiatica.ConclusionsResearch on natural medicines for AD has progressed steadily over the past two decades, with current emphasis on elucidating multi-target mechanisms using emerging technologies. However, clinical evidence remains limited. Future studies should strengthen multi-omics integration and clinical translation to foster innovative AD prevention and treatment strategies.
BackgroundArterial stiffness is an emerging risk factor for Alzheimer's disease (AD) and related dementias (ADRD) and is assessed by measuring pulse wave velocity (PWV). Recent mathematical modeling has allowed for the delineation of arterial stiffness caused by structural remodeling (S) and blood pressure, termed "load-dependent" stiffening (LD). While we recently demonstrated that S-PWV and LD-PWV are differentially associated with risk for cognitive decline and AD/ADRD brain imaging biomarkers, the associations between paired measures of S-PWV and LD-PWV with cognitive function, AD/ADRD brain imaging biomarkers, and plasma AD biomarkers have not been assessed.ObjectiveTo conduct a comprehensive analysis combining cross-sectional data from the Wake Forest Alzheimer's Disease Research Center. We hypothesized that higher S-PWV would be associated with worse cognitive function. We also hypothesized that S-PWV and LD-PWV would be differentially associated with brain imaging biomarkers of ADRD and plasma AD biomarkers.MethodsMultivariable linear regression models were used to relate S-PWV and LD-PWV to all outcomes.ResultsAs hypothesized, higher S-PWV, but not LD-PWV, was associated with lower global cognitive function. Higher S-PWV and LD-PWV were differentially associated with AD/ADRD brain MRI biomarkers. We did not observe any significant associations with plasma or PET AD biomarkers in this cohort.ConclusionsS-PWV was associated with lower cognition, while S-PWV and LD-PWV were differentially associated with brain MRI biomarkers. Interventions specifically targeting arterial stiffness may preserve cognition and brain health in AD/ADRD.
BackgroundThe decision between home-based (HC) and institutional care (IC) for Alzheimer's disease (AD) is critical for patients, families, and healthcare systems, yet evidence on long-term trade-offs remains insufficient.ObjectiveThis study comprehensively compare the 5-year clinical, economic, and family-related outcomes between HC and IC for AD patients.MethodsWe conducted a prospective-retrospective cohort study involving 252 AD patients (HC = 124; IC = 128) and their families. Outcomes included cognitive and functional status (using Mini-Mental State Examination and Barthel index), neuropsychiatric symptoms (Neuropsychiatric Inventory), medication adherence (Medication Possession Ratio and Morisky Medication Adherence Scale), healthcare costs, and family impact (Depression, Anxiety and Stress Scales and General Health Questionnaire).ResultsAnalysis revealed a critical dichotomy: HC showed better early cognitive preservation but later accelerated decline, contrasting with IC's stable trajectory. IC demonstrated superior control of harmful behaviors and prevention of consequential events, while HC was associated with more significant medical complications. Medication adherence was sustainably higher in IC but progressively deteriorated in HC. Economically, HC's lower initial direct costs were offset by substantial indirect costs, while IC incurred higher but predictable direct expenditures. Crucially, the psychological and health impact on family progressed substantially in HC but remained low and stable in IC.ConclusionsNo single care model was universally superior. The HC versus IC decision involves strategic trade-offs across clinical, economic, and family domains. These findings advocate for personalized, dynamic care models that facilitate timely transitions, guided by patient needs and family capacity, to optimize long-term outcomes for both patients and their families.
BackgroundOligodendrocyte (OL) lineage biology is increasingly recognized as a contributor to Alzheimer's disease (AD) pathophysiology, but its global knowledge structure and emerging frontiers remain unclear.ObjectiveTo map the development, major contributors, intellectual bases, and research frontiers of OL-related AD research using bibliometric and visualization approaches.MethodsEnglish-language articles and reviews published from 1990 to 2025 were retrieved from the Web of Science Core Collection on January 2, 2026. After deduplication, 1746 records were analyzed. VOSviewer 1.6.20 assessed publication output, contributors, collaborations, and citation networks. CiteSpace 6.1.6 performed keyword co-occurrence, clustering, and burst detection.ResultsAnnual publications increased from 5 in 1990 to 149 in 2025, peaking at 154 in 2024, with acceleration after 2020. The United States led in productivity and impact (684 publications; 54,075 citations). Harvard University was the most productive institution (46 publications), whereas the University of California, Los Angeles had the highest average citation impact among leading institutions (147.20 citations per publication). Acta Neuropathologica was the most productive journal (66 publications; 6548 citations). Mathys et al. was the most influential cornerstone reference. Keyword clustering was robust (Q = 0.701, S = 0.958), identifying "white matter" as the central thematic cluster.ConclusionsOL-related AD research is expanding rapidly and shifting toward white matter-centered, cell state-resolved, and multi-omics paradigms. Future priorities include defining OL and oligodendrocyte precursor cell transcriptional states, clarifying myelin vulnerability and repair mechanisms, and linking OL pathology to amyloid-related processes.
BackgroundAlzheimer's disease and related dementias (ADRD) were the sixth leading cause of death among people aged 65 + in 2022 and are currently the leading cause of disability and morbidity in older adults. In 2025, an estimated 7.2 million Americans aged 65 years and older were living with Alzheimer's disease (AD), with prevalence projected to rise.ObjectiveWe describe 1) the trends in the adoption of ADRD policies that were implemented in the U.S. from 2008-2020, as well as 2) the trends in ADRD mortality during 1999-2022.MethodsWe presented mortality data for the age-adjusted rate of ADRD mortality per 100,000 people in 1999-2022 from the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research (CDC WONDER). We also collected policy data from state websites from 2008-2020.ResultsPolicies were implemented for all 50 states, starting in 2008 and ending in 2020. ADRD mortality steadily rose during 1999-2022. The first states to implement ADRD in 2008 were Iowa and Kentucky. The largest number of states added policies in 2013. South Dakota, Wyoming, Ohio, and Kansas were the last states to implement policies.ConclusionsOur study documented that all the states in the United States implemented a policy to reduce ADRD cases. We also observed that ADRD mortality steadily rose between 1999 and 2022. This rise may reflect increased reporting of ADRD as a cause of death, or policies needing more time to meet national reduction goals.
BackgroundAlzheimer's disease (AD) is commonly treated with memantine alone or in combination with cholinesterase inhibitors (ChEIs) or second-generation antipsychotics (SGAs), but the safety of these combinations remains unclear.ObjectiveTo characterize FDA Adverse Event Reporting System (FAERS)-based signals of disproportionate reporting associated with memantine-based combination therapies in patients with AD.MethodsA disproportionality analysis was conducted using data from FAERS from 2014Q1 to 2025Q2 via the MY FAERS platform. Reporting odds ratios (RORs) with 95% confidence intervals (CI) were calculated to identify safety signals. Sensitivity analyses were conducted using ChEIs or SGAs monotherapy as reference groups to assess the robustness.Results2531 patients prescribed memantine were identified, comprising memantine monotherapy (n = 1965), memantine-ChEIs combination (n = 482), and memantine-SGAs combination (n = 84). Compared to memantine monotherapy, the memantine- ChEIs combination showed disproportionate reporting signals for skin (ROR, 3.46; 95% CI, 2.05-5.85), gastrointestinal (ROR, 2.53; 95% CI, 1.92-3.33), musculoskeletal (ROR, 2.13; 95% CI, 1.29-3.50), psychiatric (ROR, 1.60; 95% CI, 1.27-2.00), general (ROR, 1.53; 95% CI, 1.18-1.97), and nervous system disorders (ROR, 1.48; 95% CI, 1.19-1.84). The memantine-SGAs combination was strongly associated with the signals of general (ROR, 3.97; 95% CI, 1.74-9.05), psychiatric (ROR, 2.14; 95% CI, 1.32-3.49), nervous system disorders (ROR, 2.03; 95% CI, 1.20-3.43), and hip fracture (ROR, 15.84; 95% CI, 3.72-67.41). Sensitivity analyses confirmed robustness across subgroups.ConclusionsMemantine-based combination therapies were associated with distinct safety signals of disproportionate reporting compared with monotherapies. These findings should be interpreted as pharmacovigilance signals that warrant cautious interpretation and further validation in well-designed observational or prospective studies.
BackgroundSex-specific vulnerability to Alzheimer's disease (AD) has been increasingly recognized, with menopause representing a decisive neuroendocrine transition. Estrogen and progesterone modulate synaptic plasticity, glucose metabolism, and amyloid-tau homeostasis, yet the impact of their decline and replacement remains controversial. AD biomarkers provide objective means to assess menopausal hormone therapy (MHT) mechanistic effects beyond cognitive endpoints.ObjectiveTo determine how MHT influences validated AD biomarkers in peri- and postmenopausal women.MethodsA systematic review was conducted following PRISMA guidelines (PROSPERO CRD420251149404). PubMed, Embase, Web of Science, and Cochrane Library were searched through September 2025 for interventional and observational studies evaluating MHT and AD biomarkers after non-surgical menopause. Eligible biomarkers included cerebrospinal fluid (CSF) and plasma markers, and amyloid-, tau- or FDG-PET imaging. Study quality was assessed using RoB-2 and ROBINS-I tools, and evidence certainty with GRADE.ResultsFourteen studies met inclusion criteria. Early or continuous transdermal 17β-estradiol was linked with lower CSF and plasma p-tau181 and preserved glucose metabolism in AD-vulnerable cortical regions. Neuroimaging studies showed decreased amyloid deposition and sustained metabolic benefits years after discontinuation. Conversely, oral conjugated equine estrogens and estrogen-progestin regimens led to neutral or unfavorable biomarker trends, particularly when initiated more than five years after menopause.ConclusionsMHT's effects on AD biomarkers depend on timing, formulation and hormonal composition. Early transdermal estradiol appears to reinforce neuroprotective biomarker profiles, whereas delayed or combined therapies may nullify these benefits. Genotype-stratified trials with harmonized biomarker reports are needed to define optimal neuroprotective windows for women.
BackgroundAlzheimer's disease (AD) is characterized by a neuropathological cascade that begins with amyloid-β (Aβ) deposition. The recent success of disease-modifying drugs targeting Aβ has demonstrated that modulating amyloidopathy can yield clinical benefits, underscoring the need for additional drugs affecting amyloid pathology.ObjectiveTo identify novel drug targets associated with Aβ accumulation in AD using Mendelian randomization (MR) analysis of the druggable genome.MethodsWe performed MR analysis on expression quantitative trait loci (eQTLs) of the druggable genome in relation to Aβ accumulation using summary-data-based MR (SMR). Blood eQTL data were obtained from the eQTLGen consortium, and brain eQTL data from BrainMeta and PsychENCODE, while Aβ positron emission tomography (PET) genome-wide association study data were derived from 11,816 non-Hispanic White participants across 13 cohorts. Co-localization analysis was conducted to enhance the reliability of the MR results, and additional validation was performed using blood and brain protein quantitative trait loci (pQTLs) as instrumental variables.ResultsThe SMR and co-localization analyses revealed causal associations between the druggable genome and Aβ accumulation, with APH1B identified in blood eQTL data and ACE, APH1B, and CR1 identified in brain eQTL data. Further analysis using pQTL data confirmed causal associations for ACE and CR1, with ACE showing a negative association with Aβ PET uptake.ConclusionsThese findings highlight potential target genes for AD treatment, and the protective effect of ACE against amyloid pathology suggests that alternative medications to ACE inhibitors may be preferred for blood pressure management in the context of AD. Overall, our study demonstrates the potential of MR to facilitate drug repurposing for AD.
Alzheimer's disease (AD) is a neurodegenerative disorder primarily characterized by cognitive decline. Its pathogenesis is complex, involving multiple pathological processes, including amyloid-β (Aβ) deposition, neuroinflammation, and synaptic dysfunction. In recent years, the role of mesenchymal stem cells (MSCs) in AD therapy has garnered significant attention. MSCs, through their multi-directional differentiation potential and paracrine effects, exhibit remarkable neuroprotective and anti-inflammatory properties, influencing AD progression. This review summarizes the potential mechanisms and effects of MSCs in AD treatment and explores precision therapeutic strategies based on MSC modulation.
Alzheimer's disease (AD) is a growing problem in our society and the most common form of dementia. This neurodegenerative disease is characterized by neuroinflammation and the accumulation of amyloid-β (Aβ) and tau. Previous studies have found associations between the oral microbiome and AD. This review aims to elucidate the role of the oral microbiome in AD, through neuroinflammation, and reviews the relationship between AD and bacteria and fungi. Studies have found bacteria (e.g., Porphyromonas gingivalis) and fungi (e.g., Candida albicans) in postmortem AD brains. Moreover, mice models have shown that oral microbes are able to cross the blood-brain barrier (BBB), and were correlated with activated microglia, neuroinflammation, and Aβ load. This review introduces a mechanistic framework that describes how oral microbes cause an inflammatory response resulting in AD pathology. Specifically, oral dysbiosis causes oral pathogens to disseminate into the bloodstream, this triggers an inflammatory response, subsequently activating microglia, ultimately resulting in AD pathology. This process can follow two pathways: First, there is a direct response of the immune system in the brain to oral pathogens that migrate through the bloodstream and cross the BBB, which causes neuroinflammation and activates microglia, leading to AD pathology. Second, an early-life systemic inflammation causes microglia to get into a "hyperactive" state, in which they respond in an exaggerated way to normal stimuli triggering immune responses throughout a person's life that result in AD pathology. This mechanistic framework provides new line of thought for future research on the question of causality of AD.
BackgroundThere is consistent evidence of a disadvantage in bilinguals' speech production compared to monolinguals in healthy individuals, but studies investigating this phenomenon in clinical populations such as mild cognitive impairment (MCI) and Alzheimer's disease (AD) are scarce. Given that both clinical groups are characterized by word-finding difficulties, understanding how bilingualism influences speech production in these populations is essential.ObjectiveTo investigate the effect of bilingualism on dominant-language speech production in individuals with MCI and AD relative to cognitively unimpaired (CU) older adults.MethodsEarly and highly proficient Catalan-Spanish bilinguals (active bilinguals) were compared to Spanish-dominant speakers with low proficiency in Catalan (passive bilinguals) using a picture-naming task. The study included 58 CU older adults, 66 patients with AD, and 124 individuals with MCI. Reaction times, accuracy, and error types were collected in the naming task in each individual's dominant language.ResultsFirst, we observed an advantage for active bilinguals compared to passive bilinguals, as indexed by faster responses, particularly for cognate words. Second, active bilinguals with MCI exhibited a disadvantage, making more naming errors than passive bilinguals with MCI, especially for non-cognates, including a higher incidence of cross-language intrusions and anomia. Third, passive bilinguals with MCI and AD showed more semantic errors than active bilinguals.ConclusionsDisadvantages in naming are discussed in terms of predictions from cognitive and linguistic theories, whereas potential advantages of speaking a second language are considered as a protective factor, consistent with frameworks such as cognitive reserve.