Biomarker Changes during 20 Years Preceding Alzheimer’s Disease

New England Journal of Medicine, Год журнала: 2024, Номер 390(8), С. 712 - 722

Опубликована: Фев. 21, 2024

Biomarker changes that occur in the period between normal cognition and diagnosis of sporadic Alzheimer's disease have not been extensively investigated longitudinal studies.

Язык: Английский

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Aggregation-Induced Emission Luminogen: Role in Biopsy for Precision Medicine

Chemical Reviews, Год журнала: 2024, Номер 124(20), С. 11242 - 11347

Опубликована: Окт. 9, 2024

Biopsy, including tissue and liquid biopsy, offers comprehensive real-time physiological pathological information for disease detection, diagnosis, monitoring. Fluorescent probes are frequently selected to obtain adequate on processes in a rapid minimally invasive manner based their advantages biopsy. However, conventional fluorescent have been found show aggregation-caused quenching (ACQ) properties, impeding greater progresses this area. Since the discovery of aggregation-induced emission luminogen (AIEgen) promoted advancements molecular bionanomaterials owing unique high quantum yield (QY) signal-to-noise ratio (SNR),

Язык: Английский

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Blood phosphorylated Tau181 reliably differentiates amyloid‐positive from amyloid‐negative subjects in the Alzheimer's disease continuum: A systematic review and meta‐analysis

Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring, Год журнала: 2025, Номер 17(1)

Опубликована: Янв. 1, 2025

Abstract INTRODUCTION Blood‐based biomarkers seem promising for the diagnosis of Alzheimer's disease (AD). METHODS We performed a systematic review and meta‐analysis on potential blood phosphorylated Tau181 (p‐tau181) to differentiate amyloid‐positive (A+) amyloid‐negative (A−) subjects. Two meta‐analyses were conducted, showing mean p‐tau values in cerebrospinal fluid (CSF) A+ A− group, second comparing concentrations CSF among versus A‐ participants, by laboratory assessment method. RESULTS Eighteen studies (2764 5646 subjects) included. The single‐group showed higher p‐tau181 than group. In head‐to‐head meta‐analysis, reliably differentiated patients from participants. DISCUSSION Regardless technique, differentiates Therefore, it might have important applications early inclusion clinical trials AD patients. Highlights role blood‐based discriminating is still uncertain. Blood distinguishes allow trials.

Язык: Английский

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Amyloid-β oligomers drive amyloid deposit and cascaded tau pathology of Alzheimer's disease in aged brains of non-human primates

Journal of genetics and genomics/Journal of Genetics and Genomics, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

Язык: Английский

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Artificial intelligence for dementia—Applied models and digital health

Alzheimer s & Dementia, Год журнала: 2023, Номер 19(12), С. 5872 - 5884

Опубликована: Июль 26, 2023

Abstract INTRODUCTION The use of applied modeling in dementia risk prediction, diagnosis, and prognostics will have substantial public health benefits, particularly as “deep phenotyping” cohorts with multi‐omics data become available. METHODS This narrative review synthesizes understanding models digital technologies, terms diagnostic discrimination, prognosis, progression. Machine learning approaches show evidence improved predictive power compared to standard clinical scores predicting dementia, the potential decompose large numbers variables into relatively few critical predictors. RESULTS focuses on key areas emerging promise including: emphasis easier, more transparent sharing cohort access; integration high‐throughput biomarker electronic record modeling; progressing beyond primary prediction secondary outcomes, for example, treatment response physical health. DISCUSSION Such benefit also from improvements remote measurement, whether cognitive (e.g., online), or naturalistic watch‐based accelerometry).

Язык: Английский

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Neuronal ApoE4 in Alzheimer’s disease and potential therapeutic targets

Frontiers in Aging Neuroscience, Год журнала: 2023, Номер 15

Опубликована: Июнь 2, 2023

The most prevalent genetic risk factor for Alzheimer’s disease (AD) is Apolipoprotein E (ApoE), a gene located on chromosome 19 that encodes three alleles (e2, e3, and e4) give rise to the ApoE subtypes E2, E3, E4, respectively. E2 E4 have been linked increased plasma triglyceride concentrations are known play critical role in lipoprotein metabolism. prominent pathological features of AD mainly include senile plaques formed by amyloid β (Aβ 42 ) aggregation neuronal fibrous tangles (NFTs), deposited composed Aβ hyperphosphorylation truncated head. In central nervous system, protein primarily derived from astrocytes, but also produced when neurons stressed or affected certain stress, injury, aging conditions. ApoE4 induces tau pathologies, leading neuroinflammation damage, impairing learning memory functions. However, how mediates pathology remains unclear. Recent studies shown may lead greater neurotoxicity, which increases development. This review focuses pathophysiology explains deposition, mechanisms hyperphosphorylation, potential therapeutic targets.

Язык: Английский

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Changes in CSF sPDGFRβ level and their association with blood–brain barrier breakdown in Alzheimer’s disease with or without small cerebrovascular lesions

Alzheimer s Research & Therapy, Год журнала: 2023, Номер 15(1)

Опубликована: Март 14, 2023

Abstract Background CSF-soluble platelet-derived growth factor receptor beta (sPDGFRβ) is closely associated with pericyte damage. However, the changes in CSF sPDGFRβ levels and their role blood – brain barrier (BBB) leakage at different stages of Alzheimer’s disease (AD), or without cerebral small vessel (CSVD) burden, remain unclear. Methods A total 158 individuals from China Aging Neurodegenerative Disorder Initiative cohort were selected, including 27, 48, 83 a clinical dementia rating (CDR) score 0, 0.5, 1 2, respectively. tau, phosphorylated tau181 (p-tau181), Aβ40, Aβ42 measured using Simoa assay. Albumin by commercial assay kits. CSVD burden was assessed magnetic resonance imaging. Results highest level CDR 0.5 group. significantly correlated CSF/serum albumin ratio (Q-alb) 0–0.5 group ( β = 0.314, p 0.008) but not 1–2 − 0.117, 0.317). In group, exhibited significant mediating effect between Aβ42/Aβ40 Q-alb 0.038). Q-alb, rather than sPDGFRβ, showed difference burden. Furthermore, higher subjects progressive mild cognitive impairment those stable < 0.001). Meanwhile, yearly MMSE scores 0.400, 0.020) (A+) subgroup 0.542, 0.019). Conclusions We provide evidence that increased BBB early stage AD, which may contribute to AD progression.

Язык: Английский

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Blood-based biomarkers for Alzheimer’s disease: a multicenter-based cross-sectional and longitudinal study in China

Science Bulletin, Год журнала: 2023, Номер 68(16), С. 1800 - 1808

Опубликована: Июль 11, 2023

Discrepancies in diagnostic biomarkers for Alzheimer's Disease (AD) may arise from racial disparities, risk factors, or lifestyle differences. Moreover, there has been a lack of systematic and multicenter studies to evaluate baselines the AD Chinese populations. Thus, is an urgent need research investigate effectiveness blood AD, specifically Han population, using approach. In present multicenter-based cross-sectional longitudinal study, we evaluated 817 samples 6 different clinical centers. We measured plasma amyloid beta (Aβ)-40, Aβ42, phosphorylated tau 181 (pTau), total (tTau), serum neurofilament light (NFL), glial fibrillary acidic protein (GFAP). Additionally, 18F-florbetapir positron electron tomography magnetic resonance imaging were also performed. A combination APOE genotype with pTau GFAP demonstrated exceptional performance distinguishing Aβ status. Furthermore, baseline levels exhibited strong association cognitive decline over time brain atrophy, higher predicting faster rate neurodegeneration. summary, these results validate practicality encompassing various regions within China. they emphasize potential as non-invasive methods detecting screening at early stage.

Язык: Английский

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Pathophysiology characterization of Alzheimer’s disease in South China’s aging population: for the Greater-Bay-Area Healthy Aging Brain Study (GHABS)

Alzheimer s Research & Therapy, Год журнала: 2024, Номер 16(1)

Опубликована: Апрель 16, 2024

Abstract Introduction The Guangdong-Hong Kong-Macao Greater-Bay-Area of South China has an 86 million population and faces a significant challenge Alzheimer’s disease (AD). However, the characteristics prevalence AD in this area are still unclear due to rarely available community-based neuroimaging cohort. Methods Following standard protocols Disease Neuroimaging Initiative, Healthy Aging Brain Study (GHABS) was initiated 2021. GHABS participants completed clinical assessments, plasma biomarkers, genotyping, magnetic resonance imaging (MRI), β-amyloid (Aβ) positron emission tomography (PET) imaging, tau PET imaging. cohort focuses on pathophysiology characterization early detection Greater Bay Area. In study, we analyzed Aβ 42 /Aβ 40 (A), p-Tau 181 (T), neurofilament light, GFAP by Simoa 470 Chinese older adults, 301, 195, 70 had MRI, PET, respectively. Plasma hippocampal volume, temporal-metaROI cortical thickness were compared between normal control (NC), subjective cognitive decline (SCD), mild impairment (MCI), dementia groups, controlling for age, sex, APOE-ε4 . A/T profiles positivity also determined different diagnostic groups. Results aims, study design, data collection, potential applications summarized. SCD individuals significantly higher than NC individuals. MCI patients showed more abnormal changes all biomarkers frequencies A+/T+ (NC; 5.9%, SCD: 8.2%, MCI: 25.3%, dementia: 64.9%) (NC: 25.6%, 22.5%, 47.7%, 89.3%) reported. Discussion may provide helpful guidance toward designing community cohorts China. This first time, reported atrophy, AD-signature thinning, as well Area These findings novel insights into understanding pathological China’s population.

Язык: Английский

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Astrocyte reactivity is associated with tau tangle load and cortical thinning in Alzheimer’s disease

Molecular Neurodegeneration, Год журнала: 2024, Номер 19(1)

Опубликована: Июль 30, 2024

Abstract Background It is not fully established whether plasma β-amyloid(Aβ) 42 /Aβ 40 and phosphorylated Tau 181 (p-Tau ) can effectively detect Alzheimer’s disease (AD) pathophysiology in older Chinese adults how these biomarkers correlate with astrocyte reactivity, Aβ plaque deposition, tau tangle aggregation, neurodegeneration. Methods We recruited 470 analyzed , p-Tau glial fibrillary acidic protein (GFAP), neurofilament light (NfL) using the Simoa platform. Among them, 301, 195, 70 underwent magnetic resonance imaging, positron emission tomography imaging. The thresholds were defined as ≤0.0609 ≥2.418 based on receiver operating characteristic curve analysis Youden index by comparing Aβ-PET negative cognitively unimpaired individuals positive impaired patients. To evaluate feasibility of (A) (T) to AD understand reactivity affects this process, we compared GFAP, plaque, tangle, NfL, hippocampal volume, temporal-metaROI cortical thickness between different A/T profiles explored their relations each other general linear models, including age, sex, APOE-ε4 diagnosis covariates. Results Plasma A+/T + showed highest levels axonal degeneration, lowest volume thickness. Lower higher independently synergistically correlated GFAP plaque. Elevated concentrations directly interactively associated more formation. Regarding neurodegeneration, strongly measured lower related greater atrophy. Higher thinner significantly interacted predicting thinning. Voxel-wise imaging confirmed findings. Discussion This study provides a valuable reference for community population offers novel insights into contributes progression, highlighting importance targeting reactive astrogliosis prevent AD.

Язык: Английский

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