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The glymphatic system as a brain scavenger in Alzheimer's disease: mechanisms and therapeutic implications - PubMed
2 months ago
- The glymphatic system acts as a brain scavenger, clearing waste like amyloid-β (Aβ) and tau proteins.
- Glymphatic dysfunction in Alzheimer's disease (AD) leads to toxic protein accumulation, driving disease progression.
- Astrocytes and microglia play key roles in regulating glymphatic function via AQP4 channels and phagocytosis.
- Loss of AQP4 polarization, fluid exchange obstruction, and microglial dysregulation worsen AD pathology.
- Diagnostic advances (Aβ/tau PET imaging, CSF biomarkers) enable early AD detection.
- Therapeutic strategies targeting glymphatic-astrocyte-microglia interactions (AQP4 enhancers, TREM2 agonists) show promise.
Epidemiological trends and cross-country inequalities in the global burden of Alzheimer's disease and other dementias in postmenopausal women from 1990 to 2021 - PubMed
2 months ago
- The study evaluates the global burden of Alzheimer's disease and other dementias (ADOD) in postmenopausal women from 1990 to 2021, projecting trends to 2050.
- Key metrics include age-standardized rates (ASRs) for prevalence, incidence, mortality, and disability-adjusted life-years (DALYs), with East Asia showing the highest prevalence and incidence, and Central Sub-Saharan Africa the highest mortality and DALYs.
- Population growth (82.07%) and aging (12.48%) were the main drivers of increased DALYs globally from 1990 to 2021.
- Socio-demographic index (SDI)-related inequalities widened, with higher SDI countries bearing a disproportionately higher ADOD burden.
- Projections to 2050 indicate continued increases in ADOD burden, with high fasting plasma glucose identified as the leading risk factor.
- The findings emphasize the need for proactive prevention strategies, including targeted health policies and glucose control, to address the growing ADOD burden in postmenopausal women.
The evolving landscape of amyloid-targeting therapies in Alzheimer's disease: progress and challenges - PubMed
2 months ago
- Alzheimer's disease (AD) is the leading cause of dementia worldwide.
- Amyloid-β (Aβ) accumulation has guided therapeutic development, but early inhibitors failed to show clinical benefits.
- Monoclonal antibodies like aducanumab, lecanemab, and donanemab show significant amyloid clearance and modest cognitive decline slowing in Phase 3 trials.
- Clinical benefits of amyloid-targeting therapies are limited, with safety concerns like amyloid-related imaging abnormalities (ARIA) and high costs.
- The multifactorial pathology of AD, including tau, neuroinflammation, and vascular dysfunction, presents persistent therapeutic gaps.
- Amyloid-targeting therapies are the first validated disease-modifying strategy for AD but are not definitive solutions.
- Future directions include earlier intervention, combination therapies, improved antibody design, and scalable biomarker implementation.
Metformin provides superior neuroprotective potential compared to semaglutide in preventing diabetes-associated Alzheimer's disease via dual actions - PubMed
2 months ago
- Metformin shows superior neuroprotective potential compared to semaglutide in preventing diabetes-associated Alzheimer's disease (AD).
- The study used comparative network pharmacology to evaluate 39 diabetes therapies, finding metformin most effective and semaglutide least effective in AD prevention.
- Metformin's benefits are mediated through AMPK, insulin, and adipocytokine signaling, influencing key Alzheimer's-related processes.
- Certain combination therapies (e.g., insulin glargine with lixisenatide) showed effects comparable to metformin.
- The findings support prioritizing metformin for targeted studies in high-risk diabetes patients and highlight the need for precision medicine in AD prevention trials.
Increased risk of infusion-related reactions switching between monoclonal antibodies for Alzheimer's disease: A case series - PubMed
2 months ago
- Monoclonal antibodies (mAbs) targeting amyloid plaques are increasingly used in early Alzheimer's disease (AD).
- Infusion-related reactions (IRRs) are recognized class effects, but little is known about their occurrence when switching between anti-amyloid agents.
- A retrospective case series of four patients who transitioned from aducanumab to lecanemab or donanemab was performed.
- Four patients developed IRRs during or shortly after their first lecanemab infusion.
- Pre-medication reduced recurrence of IRRs in some cases during subsequent infusions.
- Prior exposure to mAbs may predispose some patients to more pronounced IRRs when switched to another agent in the class.
- Larger observational studies are needed to establish the incidence, mechanisms, and best practices for prevention and management of IRRs.
Rapamycin Reduces Amyloid-β Plaques and Improves Behavioral Performance in a Sex-Dependent Manner in Mouse Models of Amyloidosis - PubMed
2 months ago
- Rapamycin reduces amyloid-β plaques and improves behavioral performance in mouse models of amyloidosis.
- Effects of rapamycin are more pronounced in female mice.
- Rapamycin enhances microglial lysosomal degradation and promotes Aβ phagocytic clearance.
- The study highlights rapamycin's therapeutic potential in Alzheimer's disease treatment.
Head-to-head comparison of brain-derived pTau217 and total pTau217 for brain amyloid and tau pathology classification - PubMed
2 months ago
- pTau217 is a promising blood-based biomarker for Alzheimer's disease (AD) detection.
- Brain-derived pTau217 (BD-pTau217) shows higher specificity for AD-related brain changes compared to total pTau217.
- BD-pTau217 has less interference from kidney dysfunction than total pTau217.
- BD-pTau217 correlates more strongly with amyloid-PET Centiloid values than total pTau217.
- BD-pTau217 outperforms total pTau217 in classifying amyloid-β (Aβ) pathology and identifying tau-positive individuals.
- The study suggests BD-pTau217 as a superior biomarker for early detection and staging of AD.
Healthy lifestyle and Alzheimer's disease in individuals with hyperlipidemia: A prospective cohort study - PubMed
2 months ago
- The study investigates the association between healthy lifestyle behaviors and Alzheimer's disease (AD) risk in individuals with hyperlipidemia.
- A cohort of 241,642 dementia-free participants from the UK Biobank was analyzed, with a median follow-up of 14.5 years.
- A weighted lifestyle score (0-7) was used, derived from seven factors, and categorized into five tiers.
- Hyperlipidemia was defined as lipid-lowering medication use or LDL-cholesterol ≥ 4.0 mmol/L.
- Over the follow-up period, 1728 AD cases occurred, with 977 cases among 104,082 individuals with hyperlipidemia.
- Unhealthy lifestyle was associated with elevated AD risk (HR: 1.17; 95% CI: 1.02-1.35), while healthier tiers showed progressively lower risk (HR=0.85 and 0.74).
- The associations were significant among individuals with hyperlipidemia but not statistically significant among those without hyperlipidemia.
- The study concludes that healthy lifestyle patterns are associated with lower AD risk in individuals with hyperlipidemia, with greater risk reductions for healthier lifestyle tiers.
APOE4-dependent association between metformin use and Alzheimer's disease-related cortical thickness in older adults with type 2 diabetes - PubMed
2 months ago
- Metformin use is associated with greater Alzheimer's disease (AD)-signature cortical thickness (AD-CT) in older adults with type 2 diabetes mellitus (T2DM).
- The association between metformin use and AD-CT is moderated by APOE4 status, with benefits observed primarily in APOE4 non-carriers.
- Metformin use was not significantly associated with amyloid-β (Aβ), tau deposition, or white matter hyperintensity (WMH) volume.
- APOE4 non-carriers using metformin showed better global cognition alongside greater AD-CT.
- The study suggests metformin may have neuroprotective effects independent of amyloid or tau pathology, particularly in individuals without the APOE4 genetic risk factor.
Effect and potential mechanism of photobiomodulation therapy on cognitive deficits in animal models of Alzheimer's disease: a systematic review and meta-analysis - PubMed
2 months ago
- Photobiomodulation (PBM) therapy shows potential in improving cognitive function in Alzheimer's disease (AD) animal models.
- Meta-analysis of 16 studies indicates PBM significantly enhances learning ability and reduces Aβ deposition and p-Tau levels.
- PBM therapy enhances cytochrome c oxidase (CCO) activity, suggesting a mechanism involving mitochondrial function improvement.
- Greater cognitive improvements were observed in transgenic animal models and with specific PBM parameters (wavelength >750 nm, energy density ≤3 J/cm²).
- Preclinical evidence supports PBM's efficacy, but human translation requires optimization of treatment parameters and further high-quality trials.
SSEA3 and CD105 positivity are associated with the treatment potency of human neural crest-derived nasal turbinate stem cells for Alzheimer's disease - PubMed
2 months ago
- SSEA3 and CD105 positivity in human neural crest-derived nasal turbinate stem cells (NTSCs) are linked to their therapeutic efficacy for Alzheimer's disease (AD).
- NTSCs with higher percentages of SSEA3+/CD105+ cells (NTSCs-H) showed greater proliferative capacity, multilineage differentiation potency, and secretion of neuroprotective cytokines compared to those with lower percentages (NTSCs-L).
- Both NTSCs-H and pure SSEA3+/CD105+ cells (NTSCs-SC) improved cognitive function, reduced Aβ deposition, inflammation, and neuronal death in AD model mice and cerebral organoids.
- No significant difference in therapeutic outcomes was observed between NTSCs-H and NTSCs-SC treatments.
- SSEA3/CD105 positivity could serve as a marker for predicting the therapeutic potential of NTSCs in AD treatment.
Increased incidence of mild cognitive impairment in long COVID patients - PubMed
2 months ago
- Increased incidence of mild cognitive impairment (MCI) in Long-COVID patients compared to recovered-COVID and COVID-negative groups.
- Cumulative incidence of MCI over 4.4 years was 27% for Long-COVID, 5% for recovered-COVID, and 1% for COVID-negative subjects.
- Higher hazard of MCI in Long-COVID patients (HR 3.93) and specifically for Alzheimer's disease-related MCI subtype (HR 3.20).
- Study highlights the significant cognitive risks associated with Long-COVID, particularly concerning Alzheimer's disease-related MCI.
Altered locus coeruleus links to atrophy and hypometabolism in individuals with high Alzheimer's disease biomarkers - PubMed
2 months ago
- The locus coeruleus (LC) is the first region to show tau pathology in Alzheimer's disease (AD) and releases norepinephrine, which has neuroprotective effects.
- Study examined the relationship between LC integrity and whole-brain integrity, and how AD biomarkers may influence this relationship.
- LC intensity and volume were measured using neuromelanin-sensitive MRI in 71 cognitively unimpaired elderly individuals.
- LC intensity was directly associated with gray matter volume (GMV), while both LC intensity and volume interacted with AD biomarkers to predict GMV and glucose metabolism.
- Findings suggest that LC and gray matter alterations occur together in aging individuals with elevated AD biomarker levels.
- The study is part of the Age-Well randomized controlled trial (ClinicalTrials.gov Identifier: NCT02977819).
Exercise alleviates cognitive dysfunction in Alzheimer's disease mice via skeletal muscle-derived extracellular vesicles that enhance plaque clearance by microglia - PubMed
2 months ago
- Exercise improves cognitive function in Alzheimer's disease (AD) mice.
- Skeletal muscle-derived extracellular vesicles (SKM-EVs) play a key role in this improvement.
- SKM-EVs are taken up by microglia, enhancing amyloid-beta plaque clearance.
- miR-378a-3p in SKM-EVs regulates lipid metabolism in microglia by targeting p110α.
- Administering EVs from miR-378a-overexpressing myotubes alleviates cognitive impairment in AD mice.
- Exercise-induced SKM-EVs act as a myokine, facilitating muscle-to-brain communication.
- This study suggests a potential exercise-mimicking therapeutic strategy for AD.
Phagocytes as plaque catalysts: Human macrophages generate seeding-competent Aβ42 fibrils with cross-seeding activity - PubMed
2 months ago
- Human phagocytes, including macrophages and microglia, actively produce extracellular, seeding-competent Aβ42 fibrils, challenging the view that they only guard against Aβ accumulation in Alzheimer's disease (AD).
- These cell-generated Aβ42 fibrils differ from synthetic ones, showing enhanced seeding and tau cross-seeding activity in biosensor models.
- Aβ42 fibril formation requires active cellular processes and is worsened by the loss of TREM2, a major AD risk gene.
- Transcriptomic profiling reveals an early inflammatory response similar to microglial states in human AD models.
- The findings suggest microglia and macrophages may have a dual role in AD, acting both as responders and inadvertent facilitators of amyloid assembly, with implications for early therapeutic intervention.
Cellular circadian period and its deviation associate with Alzheimer's pathology and brain aging in cognitively impaired older adults - PubMed
2 months ago
- Cellular circadian period and its deviation (Δ-period) were measured in dermal fibroblasts from 135 older adults with cognitive complaints.
- Longer intrinsic circadian period was associated with higher levels of Alzheimer's disease (AD)-related biomarkers (pTau-217, NfL, GFAP) and medial temporal atrophy.
- Greater Δ-period was linked to older age, poorer cognitive performance, and widespread brain atrophy, indicating broader aging-related neurodegeneration.
- Both longer circadian period and greater Δ-period independently predicted faster clinical decline in older adults with cognitive concerns.
- The study suggests cellular circadian properties can serve as complementary biomarkers for AD-related tau pathology and aging-related neurodegeneration.
Lecanemab and Donanemab Combination Therapy for Alzheimer's Disease-The Cocktail May Work Even Better Together - PubMed
2 months ago
- Lecanemab and Donanemab are FDA-approved antiamyloid immunotherapies for Alzheimer's disease.
- Lecanemab targets amyloid protofibrils, while Donanemab targets amyloid plaques intracranially.
- Combination therapy of both drugs may produce an augmented effect.
- Research on combination therapy requires collaboration between pharmaceutical companies, academia, government, and advocacy groups.
Interferon-induced protein IFIT3 as a molecular nexus of neuroinflammation in Alzheimer's disease and HIV-associated neurocognitive disorders - PubMed
2 months ago
- Interferon-induced protein IFIT3 is identified as a key player in neuroinflammation in Alzheimer's disease (AD) and HIV-associated neurocognitive disorders (HAND).
- The study utilized postmortem human brain tissues from individuals with AD and HAND, sourced from the University of California, San Diego, and the National NeuroAIDS Tissue Consortium.
- The authors declare no competing interests, ensuring unbiased research findings.
- The research highlights the potential of IFIT3 as a biomarker for neuroinflammation in these neurodegenerative conditions.
- References include recent studies on Alzheimer's disease pathophysiology, diagnostic techniques, and the role of AI in understanding nutritional influences on AD mortality.
Modulating LRP1 Pathways in Alzheimer's Disease: Mechanistic Insights and Emerging Therapies - PubMed
2 months ago
- Alzheimer's disease (AD) is the leading cause of dementia globally, characterized by amyloid β (Aβ) accumulation, tau hyperphosphorylation, and neuroinflammation.
- Low-density lipoprotein receptor-related protein 1 (LRP1) is a promising therapeutic target due to its role in Aβ efflux, tau control, and neurovascular maintenance.
- LRP1 deficiency in AD worsens clearance, vascular impairment, and neurodegeneration.
- Emerging therapies include ligand-functionalized nanocarriers, antibodies, gene manipulation, and strategies like upregulating hepatic LRP1 or modulating cofactors like ANKS1A.
- Challenges include lower receptor expression, systemic off-target effects, and blood-brain barrier (BBB) penetration.
- Innovative approaches include engineered nanoparticles, ApoE4 interaction prevention, and endothelial-targeted gene therapy.
- LRP1 modulation is repositioned as a multifaceted therapeutic gateway for AD.
Fisetin targets multiple signaling pathways to suppress microglia-mediated neuroinflammation and cognitive decline in Alzheimer's disease - PubMed
2 months ago
- Fisetin improves cognitive performance in APP/PS1 mice and reduces amyloid pathology.
- Fisetin inhibits pro-inflammatory activation in microglia and reduces mitochondrial ROS overproduction.
- PI3K identified as a key signaling node in fisetin's regulation of microglial inflammatory responses.
- Fisetin modulates the PI3K-Akt-NF-κB axis to limit NF-κB nuclear translocation and cytokine release.
- Conditioned medium from fisetin-treated microglia alleviates neuronal damage and restores BDNF and PSD95 expression.
- PI3K may act as a molecular target of fisetin, highlighting its therapeutic potential in Alzheimer's disease.

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#alzheimer's disease

The glymphatic system as a brain scavenger in Alzheimer's disease: mechanisms and therapeutic implications - PubMed

Epidemiological trends and cross-country inequalities in the global burden of Alzheimer's disease and other dementias in postmenopausal women from 1990 to 2021 - PubMed

The evolving landscape of amyloid-targeting therapies in Alzheimer's disease: progress and challenges - PubMed

Metformin provides superior neuroprotective potential compared to semaglutide in preventing diabetes-associated Alzheimer's disease via dual actions - PubMed

Increased risk of infusion-related reactions switching between monoclonal antibodies for Alzheimer's disease: A case series - PubMed

Rapamycin Reduces Amyloid-β Plaques and Improves Behavioral Performance in a Sex-Dependent Manner in Mouse Models of Amyloidosis - PubMed

Head-to-head comparison of brain-derived pTau217 and total pTau217 for brain amyloid and tau pathology classification - PubMed

Healthy lifestyle and Alzheimer's disease in individuals with hyperlipidemia: A prospective cohort study - PubMed

APOE4-dependent association between metformin use and Alzheimer's disease-related cortical thickness in older adults with type 2 diabetes - PubMed

Effect and potential mechanism of photobiomodulation therapy on cognitive deficits in animal models of Alzheimer's disease: a systematic review and meta-analysis - PubMed

SSEA3 and CD105 positivity are associated with the treatment potency of human neural crest-derived nasal turbinate stem cells for Alzheimer's disease - PubMed

Increased incidence of mild cognitive impairment in long COVID patients - PubMed

Altered locus coeruleus links to atrophy and hypometabolism in individuals with high Alzheimer's disease biomarkers - PubMed

Exercise alleviates cognitive dysfunction in Alzheimer's disease mice via skeletal muscle-derived extracellular vesicles that enhance plaque clearance by microglia - PubMed

Phagocytes as plaque catalysts: Human macrophages generate seeding-competent Aβ42 fibrils with cross-seeding activity - PubMed

Cellular circadian period and its deviation associate with Alzheimer's pathology and brain aging in cognitively impaired older adults - PubMed

Lecanemab and Donanemab Combination Therapy for Alzheimer's Disease-The Cocktail May Work Even Better Together - PubMed

Interferon-induced protein IFIT3 as a molecular nexus of neuroinflammation in Alzheimer's disease and HIV-associated neurocognitive disorders - PubMed

Modulating LRP1 Pathways in Alzheimer's Disease: Mechanistic Insights and Emerging Therapies - PubMed

Fisetin targets multiple signaling pathways to suppress microglia-mediated neuroinflammation and cognitive decline in Alzheimer's disease - PubMed