Alzheimer's disease pathophysiology in the Retina

Progress in Retinal and Eye Research, Journal Year: 2024, Volume and Issue: 101, P. 101273 - 101273

Published: May 15, 2024

The retina is an emerging CNS target for potential noninvasive diagnosis and tracking of Alzheimer's disease (AD). Studies have identified the pathological hallmarks AD, including amyloid β-protein (Aβ) deposits abnormal tau protein isoforms, in retinas AD patients animal models. Moreover, structural functional vascular abnormalities such as reduced blood flow, Aβ deposition, blood-retinal barrier damage, along with inflammation neurodegeneration, been described mild cognitive impairment dementia. Histological, biochemical, clinical studies demonstrated that nature severity pathologies brain correspond. Proteomics analysis revealed a similar pattern dysregulated proteins biological pathways patients, enhanced inflammatory neurodegenerative processes, impaired oxidative-phosphorylation, mitochondrial dysfunction. Notably, investigational imaging technologies can now detect AD-specific deposits, well vasculopathy neurodegeneration living suggesting alterations at different stages links to pathology. Current exploratory ophthalmic modalities, optical coherence tomography (OCT), OCT-angiography, confocal scanning laser ophthalmoscopy, hyperspectral imaging, may offer promise assessment AD. However, further research needed deepen our understanding AD's impact on its progression. To advance this field, future require replication larger diverse cohorts confirmed biomarkers standardized retinal techniques. This will validate aiding early screening monitoring.

Language: Английский

---

Astrocyte biomarkers GFAP and YKL‐40 mediate early Alzheimer's disease progression

Alzheimer s & Dementia, Journal Year: 2023, Volume and Issue: 20(1), P. 483 - 493

Published: Sept. 10, 2023

Abstract INTRODUCTION We studied how biomarkers of reactive astrogliosis mediate the pathogenic cascade in earliest Alzheimer's disease (AD) stages. METHODS performed path analysis on data from 384 cognitively unimpaired individuals ALzheimer and FAmilies (ALFA)+ study using structural equation modeling to quantify relationships between AD pathological cascade. RESULTS Cerebrospinal fluid (CSF) amyloid beta (Aβ) 42/40 was associated with Aβ aggregation positron emission tomography (PET) CSF p‐tau 181 , which turn directly neurofilament light (NfL). Plasma glial fibrillary acidic protein (GFAP) mediated relationship Aβ‐PET, YKL‐40 partly explained association NfL. DISCUSSION Our results suggest that astrogliosis, as indicated by different biomarkers, influences during preclinical stage AD. While plasma GFAP mediates early soluble insoluble Aβ, latter downstream Aβ‐induced tau pathology tau‐induced neuronal injury. Highlights Lower linked higher concentrations. partially Aβ. phosphorylation

Language: Английский

---

A critical appraisal of blood-based biomarkers for Alzheimer’s disease

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 96, P. 102290 - 102290

Published: April 1, 2024

Language: Английский

---

Blood Astrocyte Biomarkers in Alzheimer Disease

Neurology, Journal Year: 2024, Volume and Issue: 103(3)

Published: July 10, 2024

Neuroinflammation, particularly early astrocyte reactivity, is a significant driver of Alzheimer disease (AD) pathogenesis. It unclear how the levels biomarkers change in patients across AD continuum and which best reflect AD-related change. We performed systematic review meta-analysis 3 blood (glial fibrillary acidic protein [GFAP], chitinase-3-like 1 [YKL-40], S100B) clinically diagnosed with AD.

Language: Английский

---

Brain inflammation co-localizes highly with tau in mild cognitive impairment due to early-onset Alzheimer’s disease

Brain, Journal Year: 2024, Volume and Issue: 148(1), P. 119 - 132

Published: July 16, 2024

Brain inflammation, with an increased density of microglia and macrophages, is important component Alzheimer's disease a potential therapeutic target. However, it incompletely characterized, particularly in patients whose begins before the age 65 years and, thus, have few co-pathologies. Inflammation has been usefully imaged translocator protein (TSPO) PET, but most inflammation PET tracers cannot image subjects low-binder TSPO rs6971 genotype. In development, participants any genotype can be novel tracer, 11C-ER176, that high binding more favourable metabolite profile than other currently available. We applied 11C-ER176 to detect brain mild cognitive impairment (MCI) caused by early-onset disease. Furthermore, we sought correlate localization volume loss, elevated amyloid-β (Aβ)and tau. studied 25 amnestic MCI (average 59 ± 4.5 years, 10 female) 23 healthy controls 6.0 12 female), both groups similar proportion all three TSPO-binding affinities. total distribution (VT), obtained arterial input function, was compared across using voxel-wise region-wise analyses. addition had Aβ (n = 23) tau 21). For tracers, standard uptake value ratios were calculated cerebellar grey matter as region reference. Regional correlations among determined. Data corrected for partial effect. Cognitive performance neuropsychological tools. disease, there default network, reaching statistical significance precuneus lateral temporal parietal association cortex bilaterally, right amygdala. Topographically, co-localized strongly (r 0.63 0.24). This correlation higher co-localization 0.55 0.25) (0.43 0.22). least atrophy (-0.29 0.26). These regional could detected polymorphisms. disease-related regions correlated impaired scores. Our data highlight importance target, process. they support notion that, shown experimental tissue animal models, propagation humans associated inflammation.

Language: Английский

---

Molecular biomarkers of glial activation and injury in epilepsy

Drug Discovery Today, Journal Year: 2025, Volume and Issue: unknown, P. 104289 - 104289

Published: Jan. 1, 2025

Increasing evidence from fluid biopsies suggests activation and injury of glial cells in epilepsy. The prevalence clinical subclinical seizures neurodegenerative conditions such as Alzheimer's disease, frontotemporal dementia, others merits review comparison the effects on markers epilepsy diseases with concomitant seizures. Herein, we revisit preclinical reports alterations proteins cerebrospinal blood associated various types We consider shared distinct characteristics changes different age groups sexes, humans animal models epilepsy, compare them those reported biofluids diseases. Our analysis indicates a significant overlap response these prevalent neurological conditions.

Language: Английский

---

The Common Alzheimer's Disease Research Ontology (CADRO) for biomarker categorization

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

Published: Jan. 1, 2025

Language: Английский

---

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

Molecular Neurodegeneration, Journal Year: 2024, Volume and Issue: 19(1)

Published: July 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.

Language: Английский

---

Ion transporter cascade, reactive astrogliosis and cerebrovascular diseases

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: April 9, 2024

Cerebrovascular diseases and their sequalae, such as ischemic stroke, chronic cerebral hypoperfusion, vascular dementia are significant contributors to adult disability cognitive impairment in the modern world. Astrocytes an integral part of neurovascular unit CNS play a pivotal role homeostasis, including ionic p H balance, neurotransmission, blood flow, metabolism. respond insults, inflammation, through unique molecular, morphological, functional changes, collectively known reactive astrogliosis. The function astrocytes has been subject debate. Initially, were thought primarily supportive maintaining structure nervous system. However, recent studies suggest that may have both beneficial detrimental effects. For example, can cause oligodendrocyte death demyelination. In this review, we will summarize (1) roles ion transporter cascade astrogliosis, (2) related dementias, (3) potential therapeutic approaches for dementing disorders targeting astrocytes. Understanding relationship between cascade, cerebrovascular reveal mechanisms targets development therapies brain associated with

Language: Английский

---

Recently Updated Role of Chitinase 3-like 1 on Various Cell Types as a Major Influencer of Chronic Inflammation

Cells, Journal Year: 2024, Volume and Issue: 13(8), P. 678 - 678

Published: April 14, 2024

Chitinase 3-like 1 (also known as CHI3L1 or YKL-40) is a mammalian chitinase that has no enzymatic activity, but the ability to bind chitin, polymer of N-acetylglucosamine (GlcNAc). Chitin component fungi, crustaceans, arthropods including insects and mites, parasites, it completely absent from mammals, humans mice. In general, chitin-containing organisms produce chitinases, such CHI3L1, protect body exogenous pathogens well hostile environments, was thought had similar effect in mammals. However, recent studies have revealed plays pathophysiological role by inducing anti-apoptotic activity epithelial cells macrophages. Under chronic inflammatory conditions bowel disease obstructive pulmonary disease, many groups already confirmed expression significantly induced on apical side cells, activates downstream pathways involved inflammation carcinogenesis. this review article, we summarize under various disorders discuss potential roles those cell types.

Language: Английский

---