Advances in Blood Biomarkers for Alzheimer’s Disease: Ultra-Sensitive Detection Technologies and Impact on Clinical Diagnosis DOI Open Access
Yi Zhang,

Kefan Bi,

Linfu Zhou

et al.

Degenerative Neurological and Neuromuscular Disease, Journal Year: 2024, Volume and Issue: Volume 14, P. 85 - 102

Published: July 1, 2024

Abstract: Alzheimer's disease has escalated into a critical public health concern, marked by its neurodegenerative nature that progressively diminishes cognitive abilities. Recognized as continuously advancing and presently incurable condition, AD underscores the necessity for early-stage diagnosis interventions aimed at delaying decline in mental function. Despite proven efficacy of cerebrospinal fluid positron emission tomography diagnosing AD, their broader utility is constrained significant costs invasive these procedures. Consequently, innovation blood biomarkers such Amyloid-beta, phosphorylated-tau, total-tau et al, distinguished high sensitivity, minimal invasiveness, accessibility, cost-efficiency, emerges promising avenue diagnosis. The advent ultra-sensitive detection methodologies, including single-molecule enzyme-linked immunosorbent assay immunoprecipitation-mass spectrometry, revolutionized plasma biomarkers, supplanting previous low-sensitivity techniques. This rapid advancement technology facilitates more accurate quantification pathological brain proteins AD-associated bloodstream. manuscript meticulously reviews landscape current research on immunological markers anchored National Institute Aging—Alzheimer's Association AT(N) framework. It highlights selection forefront technologies now integral to assessing markers. Additionally, this review examines crucial pre-analytical processing steps samples significantly impact outcomes addresses practical challenges faced during clinical testing. These discussions are enhancing our comprehension refining diagnostic precision using blood-based biomarkers. aims shed light potential avenues improvement techniques employed detecting investigating thereby contributing field research. Keywords: disease, blood, technologies,

Language: Английский

Biomimetic Nanovesicles as a Dual Gene Delivery System for the Synergistic Gene Therapy of Alzheimer’s Disease DOI

Sujun Jiang,

Guoen Cai, Zhimin Yang

et al.

ACS Nano, Journal Year: 2024, Volume and Issue: 18(18), P. 11753 - 11768

Published: April 22, 2024

The association between dysfunctional microglia and amyloid-β (Aβ) is a fundamental pathological event increases the speed of Alzheimer's disease (AD). Additionally, pathogenesis AD intricate single drug may not be enough to achieve satisfactory therapeutic outcome. Herein, we reported facile effective gene therapy strategy for modulation function intervention Aβ anabolism by ROS-responsive biomimetic exosome-liposome hybrid nanovesicles (designated as TSEL). codelivery β-site amyloid precursor protein cleaving enzyme-1 (BACE1) siRNA (siBACE1) TREM2 plasmid (pTREM2) efficiently penetrate blood-brain barrier enhance accumulation at lesions with help exosomes homing ability angiopep-2 peptides. Specifically, an upregulation expression can reprogram from pro-inflammatory M1 phenotype anti-inflammatory M2 while also restoring its capacity phagocytose nerve repair function. In addition, reduces production plaques source knocking out BACE1 gene, which expected further effect AD. in vivo study suggests that TSEL through synergistic two drugs ameliorate APP/PS1 mice cognitive impairment regulating activated microglial phenotype, reducing Aβ, preventing retriggering neuroinflammation. This employs delivery dual nucleic acids, achieving AD, thus offering more options treatment

Language: Английский

Citations

25
Therapeutic potential of human microglia transplantation in a chimeric model of CSF1R-related leukoencephalopathy DOI Creative Commons
Jean Paul Chadarevian, Jonathan Hasselmann, Alina Lahian

et al.

Neuron, Journal Year: 2024, Volume and Issue: 112(16), P. 2686 - 2707.e8

Published: June 18, 2024

Microglia replacement strategies are increasingly being considered for the treatment of primary microgliopathies like adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP). However, available mouse models fail to recapitulate diverse neuropathologies reduced microglia numbers observed in patients. In this study, we generated a xenotolerant model lacking fms-intronic regulatory element (FIRE) enhancer within Csf1r, which develops nearly all hallmark pathologies associated ALSP. Remarkably, transplantation human induced pluripotent stem cell (iPSC)-derived microglial (iMG) progenitors restores homeostatic signature prevents development spheroids, white matter abnormalities, reactive astrocytosis, brain calcifications. Furthermore, CRISPR-corrected ALSP-patient-derived iMG reverses pre-existing astrogliosis, calcification pathologies. Together accompanying study by Munro colleagues, our results demonstrate utility FIRE mice ALSP provide compelling evidence that could offer promising new therapeutic strategy perhaps other microglia-associated neurological disorders.

Language: Английский

Citations

23
Neuroinflammation in Alzheimer disease DOI
Wiesje M. van der Flier, Wiesje M. van der Flier,

Frank Jessen

et al.

Nature reviews. Immunology, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 9, 2024

Language: Английский

Citations

18
Plasma proteomic evidence for increased β-amyloid pathology after SARS-CoV-2 infection DOI Creative Commons
Eugene Duff,

Henrik Zetterberg,

Amanda Heslegrave

et al.

Nature Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 30, 2025

Abstract Previous studies have suggested that systemic viral infections may increase risks of dementia. Whether this holds true for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is unknown. Determining important anticipating the potential future incidence To begin to do this, we measured plasma biomarkers linked Alzheimer’s disease pathology in UK Biobank before and after serology-confirmed SARS-CoV-2 infections. infection was associated with β-amyloid pathology: reduced Aβ42:Aβ40 ratio and, more vulnerable participants, lower Aβ42 higher pTau-181. The biomarker changes were greater participants who had been hospitalized COVID-19 or reported hypertension previously. We showed brain structural imaging patterns disease, cognitive test scores poorer overall health evaluations. Our data from post hoc case–control matched study thus provide observational evidence can be older adults. While these results not establish causality, they suggest (and possibly other inflammatory diseases) risk disease.

Language: Английский

Citations

2
The Common Alzheimer's Disease Research Ontology (CADRO) for biomarker categorization DOI Creative Commons
Amanda M. Leisgang Osse,

Jefferson W. Kinney,

Jeffrey L. Cummings

et al.

Alzheimer s & Dementia Translational Research & Clinical Interventions, Journal Year: 2025, Volume and Issue: 11(1)

Published: Jan. 1, 2025

Language: Английский

Citations

2
Challenges in the practical implementation of blood biomarkers for Alzheimer’s disease DOI Creative Commons
Michael Schöll, Inge M.W. Verberk, Marta del Campo

et al.

The Lancet Healthy Longevity, Journal Year: 2024, Volume and Issue: 5(10), P. 100630 - 100630

Published: Oct. 1, 2024

Language: Английский

Citations

13
Risk of Alzheimer's disease is associated with longitudinal changes in plasma biomarkers in the multi‐ethnic Washington Heights–Hamilton Heights–Inwood Columbia Aging Project (WHICAP) cohort DOI Creative Commons
Yian Gu, Lawrence S. Honig, Min Suk Kang

et al.

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: 20(3), P. 1988 - 1999

Published: Jan. 6, 2024

Abstract BACKGROUND Alzheimer's disease (AD) biomarkers can help differentiate cognitively unimpaired (CU) individuals from mild cognitive impairment (MCI) and dementia. The role of AD in predicting needs examination. METHODS In 628 CU a multi‐ethnic cohort, amyloid beta (Aβ)42, Aβ40, phosphorylated tau‐181 (p‐tau181), glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL) were measured plasma. RESULTS Higher baseline levels p‐tau181/Aβ42 ratio associated with an increased risk incident A biomarker pattern (with elevated Aβ42/Aβ40 but low p‐tau181/Aβ42) was decreased dementia risk. Compared to CU, participants who developed MCI or had rapid decrease this protective reflecting AD‐specific pathological change. DISCUSSION Elevated p‐tau181/Aβ42, by itself combined level, predicts clinically diagnosed AD. Individuals change these may need close monitoring for the potential downward trajectory cognition. Highlights We discuss multi‐ethnic, urban community study elderly individuals. consisted longitudinal assessment over 6 years repeated clinical assessments. used blood‐based as predictors disease.

Language: Английский

Citations

11
Longitudinal plasma phosphorylated‐tau217 and other related biomarkers in a non‐demented Alzheimer's risk‐enhanced sample DOI Creative Commons

Lianlian Du,

Rebecca E. Langhough,

Rachael E. Wilson

et al.

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: 20(9), P. 6183 - 6204

Published: July 5, 2024

Abstract INTRODUCTION Understanding longitudinal change in key plasma biomarkers will aid detecting presymptomatic Alzheimer's disease (AD). METHODS Serial samples from 424 Wisconsin Registry for Prevention participants were analyzed phosphorylated‐tau217 (p‐tau217; ALZpath) and other AD biomarkers, to study trajectories relation disease, health factors, cognitive decline. Of the participants, 18.6% with known amyloid status positive (A+); 97.2% cognitively unimpaired (CU). RESULTS In CU, amyloid‐negative (A–) subset, p‐tau217 levels increased modestly age but unaffected by body mass index kidney function. whole sample, average rates higher those who A+ (e.g., simple slopes(se) A– at 60 0.232(0.028) 0.038(0.013))). High baseline predicted faster preclinical DISCUSSION stands out among markers its strong association decline, indicating potential early detection monitoring progression. Highlights Phosphorylated‐tau217 (p‐tau217) significantly different people be positive. Subtle age‐related seen all unimpaired. Kidney function not associated trajectories. Higher was

Language: Английский

Citations

10
Plasma S100β is a predictor for pathology and cognitive decline in Alzheimer’s disease DOI Creative Commons
Geetika Nehra, Bryan Maloney,

Rebecca Smith

et al.

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

Citations

1
Modulating Neuroinflammation as a Prospective Therapeutic Target in Alzheimer’s Disease DOI Creative Commons

Eunshil Lee,

Yongmin Chang

Cells, Journal Year: 2025, Volume and Issue: 14(3), P. 168 - 168

Published: Jan. 22, 2025

The recent approval of lecanemab highlights that the amyloid beta (Aβ) protein is an important pathological target in Alzheimer’s disease (AD) and further emphasizes significance neuroinflammatory pathways regulating Aβ accumulation. Indeed, accumulation triggers microglia activation, which are key mediators neuroinflammation. inflammatory responses this process can lead to neuronal damage functional decline. Microglia secrete proinflammatory cytokines accelerate death release anti-inflammatory growth factors contributing recovery protection. Thus, play a dual role neurodegeneration neuroprotection, complicating their function AD. Therefore, elucidating complex interactions between protein, microglia, neuroinflammation essential for developing new strategies treating This review investigates receptors involved activating aims enhance understanding how these processes impact AD, as well they be regulated. also analyzed studies reported existing literature ongoing clinical trials. Overall, will contribute regulatory mechanisms therapies slow progression

Language: Английский

Citations

1