The link between gut microbiome and Alzheimer's disease: From the perspective of new revised criteria for diagnosis and staging of Alzheimer's disease

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: 20(8), P. 5771 - 5788

Published: June 28, 2024

Abstract Over the past decades, accumulating evidence suggests that gut microbiome exerts a key role in Alzheimer's disease (AD). The Association Workgroup is updating diagnostic criteria for AD, which changed profiles and categorization of biomarkers from “AT(N)” to “ATNIVS.” Previously, most studies focus on correlation between amyloid beta deposition (“A”), initial AD pathological feature triggering “downstream” tauopathy neurodegeneration. However, limited research investigated interactions other pathogenesis (“TNIVS”). In this review, we summarize current findings microbial characteristics whole spectrum AD. Then, describe association with updated biomarker categories pathogenesis. addition, outline microbiome‐related therapeutic strategies Finally, discuss issues field future directions. Highlights new revised (AD) proposed by have associations are described. Current summarized. Therapeutic based proposed.

Language: Английский

---

Plasma S100β is a predictor for pathology and cognitive decline in Alzheimer’s disease

Fluids and Barriers of the CNS, Journal Year: 2025, Volume and Issue: 22(1)

Published: Jan. 9, 2025

Blood–brain barrier dysfunction is one characteristic of Alzheimer's disease (AD) and recognized as both a cause consequence the pathological cascade leading to cognitive decline. The goal this study was assess markers for in postmortem tissue samples from research participants who were either cognitively normal individuals (CNI) or diagnosed with AD at time autopsy determine what extent these are associated neuropathologic changes (ADNC) impairment. We used brain plasma 19 participants: 9 CNI 10 dementia patients had come University Kentucky Research Center (UK-ADRC) community-based cohort; all cases confirmed severe ADNC. Plasma obtained within 2 years autopsy. Aβ40, Aβ42, tau levels quantified by ELISA. Cortical sections cleared using X-CLARITY™ system immunostained neurovascular unit-related proteins. Brain slices then imaged confocal microscopy analyzed microvascular diameters immunoreactivity coverage Fiji/ImageJ. Isolated human microvessels assayed tight-junction protein expression JESS™ automated Western blot system. S100 calcium-binding B (S100β), matrix metalloproteinase (MMP)-2, MMP-9, neuron-specific enolase (NSE) All outcomes assessed linear associations global function (MMSE, CDR) cerebral atrophy scores Pearson, polyserial, polychoric correlation, appropriate, along generalized modeling mixed-level modeling. As expected, we detected elevated Aβ pathology compared CNI. However, found no differences sections. also observed claudin-5 capillaries isolated samples. biomarker analysis showed that 12.4-fold higher S100β levels, twofold lower NSE 2.4-fold MMP-9 1.2-fold MMP-2 than Data revealed predictive Our data suggest among different relevant dysfunction, most promising diagnostic Further investigation necessary how relate whether they may predict clinical outcomes, particularly prodromal early stages AD.

Language: Английский

---

Nutrition: A non‐negligible factor in the pathogenesis and treatment of Alzheimer's disease

Alzheimer s & Dementia, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 27, 2025

Abstract Alzheimer's disease (AD) is a degenerative characterized by progressive cognitive dysfunction. The strong link between nutrition and the occurrence progression of AD pathology has been well documented. Poor nutritional status accelerates progress potentially aggravating amyloid beta (Aβ) tau deposition, exacerbating oxidative stress response, modulating microbiota–gut–brain axis, disrupting blood–brain barrier function. advanced stage tends to lead malnutrition due impairments, sensory dysfunctions, brain atrophy, behavioral psychological symptoms dementia (BPSD). This, in turn, produces vicious cycle AD. This review discusses how factors deteriorate each other from early terminal stages AD, focusing on potential different levels factors, ranging micronutrients diet patterns. provides novel insights into reducing risk delaying its progression, improving prognosis. Highlights Two‐fifths cases worldwide have attributed modifiable factors. Up ≈26% community‐dwelling patients with are malnourished, compared 7%∼76% institutionalized patients. Undernutrition effects onset, prognosis through multiple mechanisms. Various supports were confirmed be protective for via specific

Language: Английский

---

Glymphatic system clearance and Alzheimer’s disease risk: a CSF proteome-wide study

Alzheimer s Research & Therapy, Journal Year: 2025, Volume and Issue: 17(1)

Published: Jan. 31, 2025

The emerging evidence of the role glymphatic system (GS) in Alzheimer's disease (AD) provides new opportunities for intervention from earliest stages disease. aim study is to evaluate efficacy GS AD identify biomarkers. We performed a two-stage proteomic health using intravenous gadolinium-based contrast agent (GBCA) with serial T1 3T magnetic resonance imaging (MRI) individuals amnestic mild cognitive impairment (aMCI). In Stage 1 (evaluated Cohort aMCI participants (n = 11)), we correlated levels 7K cerebrospinal fluid (CSF) proteins (estimated by SOMAscan) 78 Freesurfer-segmented brain regions interest (ROIs). A total seven different were significantly associated (p-value < 6.4 × 10-4). stronger correlations identified NSUN6, GRAAK, OLFML3, ACTN2, RUXF, SHPS1 and TIM-4. pathway enrichment analysis revealed that mainly implicated neurodegenerative processes, immunity inflammation. 2, validated these results cohort (with without pathology CSF (aMCI(-) aMCI/AD( +); n 22 7, respectively) healthy controls 10). Proteomic prediction models generated each ROI. These compared demographic-only identifying aMCI(-) +) vs controls. This was repeated determine if could those both found outperform models. Our identifies linked involved immune participants.

Language: Английский

---

Biomarkers of blood–brain barrier and neurovascular unit integrity in human cognitive impairment and dementia

Alzheimer s & Dementia, Journal Year: 2025, Volume and Issue: 21(3)

Published: March 1, 2025

Abstract Blood–brain barrier (BBB) dysfunction is recognized as an early step in the development of Alzheimer's disease and related dementias (ADRD). Biomarkers are needed to monitor BBB integrity over time, better understand role neurodegeneration, potentially help define long‐term ADRD risk, effects therapeutics. In this review, we discuss current biomarkers used detect human context cognitive decline dementia. We also promising candidate fluid blood. Highlights permeability occurs during normal aging further exacerbated ADRD. vivo imaging CSF currently setting humans. review blood‐based that may represent dysfunction.

Language: Английский

---

Relationship between brain iron dynamics and blood-brain barrier function during childhood: a quantitative magnetic resonance imaging study

Fluids and Barriers of the CNS, Journal Year: 2023, Volume and Issue: 20(1)

Published: Aug. 17, 2023

Abstract Background Mounting evidence suggests that the blood-brain barrier (BBB) plays an important role in regulation of brain iron homeostasis normal development, but these imaging profiles remain to be elucidated. We aimed establish a relationship between dynamics and BBB function during childhood using combined quantitative magnetic resonance (MRI) depict both physiological systems along developmental trajectories. Methods In this single-center prospective study, consecutive outpatients, 2–180 months age, who underwent MRI (3.0-T scanner; Ingenia; Philips) January 2020 2021, were included. Children with histories preterm birth or defects, abnormalities on MRI, diagnoses included neurological diseases follow-up examinations through December 2022 excluded. addition clinical susceptibility mapping (QSM; deposition measure) diffusion-prepared pseudo-continuous arterial spin labeling (DP-pCASL; acquired. Atlas-based analyses for QSM DP-pCASL performed investigate trajectories regional their relationships. Results A total 78 children (mean 73.8 ± 61.5 [SD]; 43 boys) evaluated. Rapid progression (Δsusceptibility value) was observed first two years (globus pallidus, 1.26 0.18 [× 10 − 3 ppm/month]; substantia nigra, 0.68 0.16; thalamus, 0.15 0.04). The scattergram Δsusceptibility value water exchange rate across ( k w ) divided by cerebral blood flow well fitted sigmoidal curve model, whose inflection point differed among each deep gray-matter nucleus 2.96–3.03 [mL/100 g] −1 ; 3.12–3.15; 3.64–3.67) accordance heterogeneity accumulation. Conclusions study pediatric brains demonstrated childhood. Trial registration UMIN Clinical Trials Registry identifier: UMIN000039047, registered 6, 2020.

Language: Английский

---

Biomaterials Comprising Implantable and Dermal Drug Delivery Targeting Brain in Management of Alzheimer’s Disease: A Review

Regenerative Engineering and Translational Medicine, Journal Year: 2024, Volume and Issue: unknown

Published: March 4, 2024

Language: Английский

---

Imaging blood–brain barrier disruption in neuroinflammation and Alzheimer’s disease

Frontiers in Aging Neuroscience, Journal Year: 2023, Volume and Issue: 15

Published: March 17, 2023

The blood–brain barrier (BBB) is the neurovascular structure that regulates passage of cells and molecules to from central nervous system (CNS). Alzheimer’s disease (AD) a neurodegenerative disorder associated with gradual breakdown BBB, permitting entry plasma-derived neurotoxins, inflammatory cells, microbial pathogens into CNS. BBB permeability can be visualized directly in AD patients using imaging technologies including dynamic contrast-enhanced arterial spin labeling magnetic resonance imaging, recent studies employing these techniques have shown subtle changes stability occur prior deposition pathological hallmarks AD, senile plaques, neurofibrillary tangles. These suggest disruption may useful as an early diagnostic marker; however, also accompanied by neuroinflammation, which complicate analyses. This review will outline structural functional during pathogenesis highlight current detect changes. Advancing improve both diagnosis treatment other diseases.

Language: Английский

---

Relationship between cognitive impairment and hippocampal iron overload: a quantitative susceptibility mapping study of a rat model

NeuroImage, Journal Year: 2025, Volume and Issue: 306, P. 121006 - 121006

Published: Jan. 7, 2025

The aim of this study was to establish an iron overload rat model simulate the elevated levels in patients with thalassemia and investigate potential association between hippocampal deposition cognition. Two groups overloaded rats one group control were used for study. Morris water maze (MWM) test spatial reference memory indicated by escape latency time number MWM platform crossings. magnetic susceptibility value tissue, a measure deposition, assessed quantitative mapping (QSM) correlated performance. content tissue sections using diaminobenzidine (DAB)-enhanced Perl's Prussian blue (PPB) staining. including Group H L had higher values than group, i.e., D. In addition, longer reduced There positive correlation mean value, negative crossings latent L. This simulating showed being associated impairment memory. QSM could be quantify brain vivo, highlighting its clinical application assessing cognitive thalassemia.

Language: Английский

---

Diffusion tensor image analysis along the perivascular space and quantitative susceptibility mapping in the diagnosis and severity assessment of Parkinson’s disease

Quantitative Imaging in Medicine and Surgery, Journal Year: 2025, Volume and Issue: 15(2), P. 1411 - 1424

Published: Jan. 24, 2025

Increased iron accumulation measured by quantitative susceptibility mapping (QSM) has been observed in various brain regions, especially substantia nigra (SN), Parkinson's disease (PD). Glymphatic dysfunction evaluated diffusion tensor image analysis along the perivascular space (DTI-ALPS) PD also attracted much attention recently. This study aimed to compare and combine DTI-ALPS QSM of SN diagnosis severity assessment PD. As a case-control study, we retrospectively recruited 60 patients matched healthy controls. The index, SN, their combination were calculated further compared between two groups. Receiver operating characteristic (ROC) curves used assess diagnostic performance. We analyzed correlation Movement Disorder Society-Unified Disease Rating Scale (MDS-UPDRS) part III score with SN. average was significantly lower, whereas bilateral higher [median (interquartile range): 1.38 (1.26-1.53); 0.09 (0.07-0.10)] controls [1.52 (1.41-1.71), P<0.001; 0.08 (0.07-0.09), P=0.020]. showed area under curve (AUC) 0.801 than that (0.729) or (0.624) discriminating from Moreover, significant correlations MDS-UPDRS (rho =-0.276, P=0.034). are potential biomarkers for them may improve

Language: Английский

---