Medin synergized with vascular amyloid-beta deposits accelerates cognitive decline in Alzheimer's disease:a potential biomarker

Brain vascular dysfunction in Alzheimer s disease(AD) pathogenesis has become increasingly clea r.Accumulating evidence shows that damaged vascular,including large or small vessels and even neurovascular unit,may accelerate the neuropathological process of AD via disrupting brain hypoperfusion,aberrant angiogenesis,and neuroinflammatory response,etc.Thus,vascular dysfunction makes a substantially contribution to the cognitive decline of AD patients.

Carpal Tunnel Syndrome: A Marker for Amyloidosis

Introduction: Amyloidosis are systemic conditions and carpal tunnel syndrome (CTS) precedes the principal systemic complications and can be used as an early marker. Our objective was to determine the frequency of amyloid deposition in idiopathic CTS and its systemic impact. Methods: We retrospectively evaluated patients with CTS between September 2019 to January 2020. Samples from the anterior carpal ligament were pathologically evaluated and amyloid deposition was confirmed by apple-green birefringence on polarized light using Congo red stain. When amyloid was detected we performed genetic testing for transthyretin variants (ATTRv), immunofixation electrophoresis in serum and urine for light chains and multidisciplinary evaluation. Results: Thirty consecutive patients were included, 19 women, 11 men, mean age 70 years old (range 42 - 89 years). We identified 3 patients (10%) with amyloid deposits (mean age: 78.6 years, 2 men, 1 woman). Genetic testing for ATTRv and light chains studies were negative. During follow-up: The first patient required aortic valve replacement. The second patient developed progressive cardiac failure with syncopal episodes, atrioventricular block and atrial fibrillation and required a pacemaker and anticoagulation. The third patient had unexplained chronic edemas. The cardiac evaluation in all 3 patients revealed left ventricular hypertrophy and myocardial uptake (Perugini Score > 2) in their nuclear bone scintigraphies with technetium pyrophosphate. Two patients were treated with tafamidis and one patient died due to refractory cardiac insufficiency. Discussion: Our findings underline the importance of investigating amyloidosis in idiopathic CTS. The identification of deposits allows early diagnosis of cardiac amyloidosis leading to timely intervention and treatment.

Current perspective on amyloid aggregation accelerating properties of the artificial butter flavoring,diacetyl

The amyloid—what peptide can resist its entropic bliss?Without kinetic barricades and chaperones,most peptides would simply tumble down that precipice.The amyloid-β(Aβ) peptides are understood to underlie the hallmark pathology of Alzheimer's disease(AD) and are considered one of the causative factors for neurodegeneration and cognitive impairment.AD affects critical connected structures within the brain that are responsible for memory,language,and social behavior.

Transmission of amyloid-βpathology in humans:a perspective on clinical evidence

Transmission of misfolded amyloid-β(Aβ)aggregates between human subjects:Protein misfolding disorders are a family of diseases characterized by the accumulation of misfolded protein aggregates.These proteinaceous structures,also known as amyloids,are key drivers of fatal neurodegenerative disorders such as prion diseases,Alzheimer’s disease(AD),Parkinson’s disease,and others.

Smart electrochemical sensing of amyloid-beta to manage total Alzheimer's diseases

Need for Alzheimer's disease progression monitoring:Alzheimer's disease(AD)is an irreversible progressive brain disorder that causes severe and incurable neuro-impairment.The World Health Organization estimates that 55 million people are affected by AD dementia by 2020 which may exceed 78 million by 2030 and 139 in 2050.The estimated cost to manage AD is above US$1.3 trillion,which will further increase to US$2.8 trillion by 2030.

Role of peripheral amyloid-β aggregates in Alzheimer’s disease: mechanistic, diagnostic, and therapeutic implications

Compelling evidence demonstrates that the levels of peripheral amyloid-β(Aβ)fluctuate in Alzheimer’s disease(AD)patients.Moreover,Aβdeposits have been identified in peripheral tissues.However,the relevance of peripheral Aβ(misfolded or not)in pathological situations,and the temporal appearance of these pathological fluctuations,are not well understood.The presence of misfolded Aβin peripheral compartments raises concerns on potential inter-individual transmissions considering the well-reported prion-like properties of this disease-associated protein.The latter is supported by multiple reports demonstrating that Aβmisfolding can be transmitted between humans and experimental animals through multiple routes of exposure.In this mini-review,we discuss the potential implications of peripheral,disease-associated Aβin disease mechanisms,as well as in diagnostic and therapeutic approaches.

Design and redesign journey of a drug for transthyretin amyloidosis

The misfolding and subsequent aggregation of proteins into amyloid fibrils underlie the onset of a variety of human disorders collectively known as amyloidosis.Transthyretin(TTR)is one of the>30 amyloidogenic proteins identified to date and is associated with a group of highly debilitating and life-threatening disorders called TTR amyloidosis(ATTR).ATTR comprises senile systemic amyloidosis,which is linked to wild-type(WT)TTR aggregation,and hereditary ATTR,a dominantly inherited disorder caused by the deposition of one of over 130 TTR genetic variants.Senile systemic amyloidosis is a prevalent age-related amyloidosis,affecting up to 25%of the population over 80 years of age,and is characterized by the build-up of TTR fibrils in the myocardium.Regarding hereditary ATTR,the clinical presentation is highly heterogeneous,primarily affecting the peripheral nervous system(familial amyloid polyneuropathy-FAP)or the heart(familial amyloid cardiomyopathy).In rare cases,aggregation develops in the central nervous system,giving rise to a phenotype known as familial leptomeningeal amyloidosis(Carroll et al.,2022).

Corrigendum: Activation of autophagy by Citri Reticulatae Semen extract ameliorates amyloid-beta-induced cell death and cognition deficits in Alzheimer’s disease

In the article titled“Activation of autophagy by Citri Reticulatae Semen extract ameliorates amyloid-beta-induced cell death and cognition deficits in Alzheimer’s disease”published on pages 2467-2479,Issue 11,Volume 19 of Neural Regeneration Research(Tang et al.,2024),there are some errors in selecting the appropriate images in Figure 7 by authors during assembling the images.

Anti-amyloid antibodies in Alzheimer’s disease: what did clinical trials teach us?

Although many causes of Alzheimer’s disease(AD)may exist,both the original amyloid cascade and tau hypotheses posit that abnormal misfolding and accumulation of amyloid-β(Aβ)and tau protein is the central event causing the pathology.However,that conclusion could be only partly true,and there is conflicting evidence about the role of both proteins in AD,being able to precede and influence one another.Some researchers argue that these proteins are mere executors rather than primary causes of pathology.Therefore,there have been continuing refinements of both hypotheses,with alternative explanations proposed.Aβand tau proteins may be independently involved in specific neurotoxic pathways;yet there may be other crucial processes going on in early AD.Moreover,accumulating evidence suggests that Aβand tau act synergistically,rather than additively in disease onset(Jeremic et al.,2021,2023a).

Recurrent Transient Ischemic Attacks Revealing Cerebral Amyloid Angiopathy: A Comprehensive Case

This case report investigates the manifestation of cerebral amyloid angiopathy (CAA) through recurrent Transient Ischemic Attacks (TIAs) in an 82-year-old patient. Despite initial diagnostic complexities, cerebral angiography-MRI revealed features indicative of CAA. Symptomatic treatment resulted in improvement, but the patient later developed a fatal hematoma. The discussion navigates the intricate therapeutic landscape of repetitive TIAs in the elderly with cardiovascular risk factors, emphasizing the pivotal role of cerebral MRI and meticulous bleeding risk management. The conclusion stresses the importance of incorporating SWI sequences, specifically when suspecting a cardioembolic TIA, as a diagnostic measure to explore and exclude CAA in the differential diagnosis. This case report provides valuable insights into these challenges, highlighting the need to consider CAA in relevant cases.

Diagnostic significance of serum levels of serum amyloid A,procalcitonin,and high-mobility group box 1 in identifying necrotising enterocolitis in newborns

BACKGROUND Necrotising enterocolitis(NEC)is a critical gastrointestinal emergency affecting premature and low-birth-weight neonates.Serum amyloid A(SAA),procalcitonin(PCT),and high-mobility group box 1(HMGB1)have emerged as potential biomarkers for NEC due to their roles in inflammatory response,tissue damage,and immune regulation.AIM To evaluate the diagnostic value of SAA,PCT,and HMGB1 in the context of NEC in newborns.METHODS The study retrospectively analysed the clinical data of 48 newborns diagnosed with NEC and 50 healthy newborns admitted to the hospital.Clinical,radiological,and laboratory findings,including serum SAA,PCT,and HMGB1 Levels,were collected,and specific detection methods were used.The diagnostic value of the biomarkers was evaluated through statistical analysis,which was performed using chi-square test,t-test,correlation analysis,and receiver operating characteristic(ROC)analysis.RESULTS The study demonstrated significantly elevated levels of serum SAA,PCT,and HMGB1 Levels in newborns diagnosed with NEC compared with healthy controls.The correlation analysis indicated strong positive correlations among serum SAA,PCT,and HMGB1 Levels and the presence of NEC.ROC analysis revealed promising sensitivity and specificity for serum SAA,PCT,and HMGB1 Levels as potential diagnostic markers.The combined model of the three biomarkers demonstrating an extremely high area under the curve(0.908).CONCLUSION The diagnostic value of serum SAA,PCT,and HMGB1 Levels in NEC was highlighted.These biomarkers potentially improve the early detection,risk stratification,and clinical management of critical conditions.The findings suggest that these biomarkers may aid in timely intervention and the enhancement of outcomes for neonates affected by NEC.

Management of cerebral amyloid angiopathy and atrial fibrillation:We are still far from precision medicine

The use of anticoagulation therapy could prove to be controversial when trying to balance ischemic stroke and intracranial bleeding risks in patients with concurrent cerebral amyloid angiopathy(CAA)and atrial fibrillation(AF).In fact,CAA is an age-related cerebral vasculopathy that predisposes patients to intracerebral hemorrhage.Nevertheless,many AF patients require oral systemic dose-adjusted warfarin,direct oral anticoagulants(such as factor Xa inhibitors)or direct thrombin inhibitors to control often associated with cardioembolic stroke risk.The prevalence of both CAA and AF is expected to rise,due to the aging of the population.This clinical dilemma is becoming increasingly common.In patients with coexisting AF and CAA,the risks/benefits profile of anticoagulant therapy must be assessed for each patient individually due to the lack of a clear-cut consensus with regard to its risks in scientific literature.This review aims to provide an overview of the management of patients with concomitant AF and CAA and proposes the implementation of a risk-based decision-making algorithm.

Dysfunction of blood-brain barrier in cerebral amyloid angiopathy

Increasing evidence demonstrated that the blood-brain barrier(BBB)was involved in developing cerebral amyloid angiopathy(CAA).The BBB participates in the neurovascular coupling and regulates the transport of substances,which is closely related to neurodegenerative diseases.In CAA,the deposition of amyloid beta(Aβ)in arteries,capillaries,and arterioles of meninges and cerebral cortex results in the destruction of the BBB,chronic inflammatory response,chronic cerebral hypoperfusion,and dysfunction of the neurovascular unit,which eventually leads to neurodegeneration.At the same time,CAA is an age-related disease.Patients with CAA often have some risk factors for cerebrovascular diseases,such as hypertension and diabetes,which can further aggravate the damage to the BBB.Thus,it is of great significance to pay attention to the BBB in the pathogenesis and future intervention targets of CAA.Therefore,this manuscript reviewed the dysfunction of the BBB in CAA.

Primary imaging features and recent application of PET tracers in cerebral amyloid angiopathy

Cerebral amyloid angiopathy(CAA)is a small vessel disease of the brain characterized by the progressive deposition of amyloid-β(Aβ)plaques in the walls of cerebral blood vessels.It presents with a subtle course and sudden onset,and currently,there are no specific therapeutic interventions available.Accurate diagnosis of CAA could enable targeted interventions in the early stages of the disease,potentially mitigating the disease’s effects.Herein,we review the primary imaging biomarkers used in the diagnosis of CAA,including their mechanisms,imaging characteristics,and significance.We also provide an interpretation of the latest version(v2.0)of the Boston criteria,which are commonly used in the clinical diagnosis of CAA.Additionally,this study introduces various positron emission tomography(PET)tracers for CAA and reviews their application values in the diagnosis of CAA.

The expanding amyloid family:Structure,stability,function,and pathogenesis

The hidden world of amyloid biology has suddenly snapped into atomic-level focus,revealing over 80 amyloid protein fibrils,both pathogenic and functional.Unlike globular proteins,amyloid proteins flatten and stack into unbranched fibrils.Stranger still,a single protein sequence can adopt wildly different two-dimensional conformations,yielding distinct fibril polymorphs.

Scutellaria baicalensis stem-leaf total flavonoid reduces neuronal apoptosis induced by amyloid beta-peptide (25-35)

Scutellaria baicalensis stem-leaf total flavonoid might attenuate learning/memory impairment and neuronal loss in rats induced by amyloid beta-peptide. This study aimed to explore the effects of Scutellaria baicalensis stem-leaf total flavonoid on amyloid beta-peptide-induced neuronal apoptosis and the expression of apoptosis-related proteins in the rat hippocampus. Male Wistar rats were given intragastric administration of Scutellaria baicalensis stem-leaf total flavonoid, 50 or 100 mg/kg, once per day. On day 8 after administration, 10 pg amyloid beta-peptide （25-35） was injected into the bilateral hippocampus of rats to induce neuronal apoptosis. On day 20, hippocampal tissue was harvested and probed with the terminal deoxyribonucleotidyl transferase-mediated biotin-16-dUTP nick-end labeling assay. Scutellaria baicalensis stem-leaf total flavonoid at 50 and 100 mg/kg reduced neuronal apoptosis induced by amyloid beta-peptide （25-35） in the rat hippocampus. Immunohistochemistry and western blot assay revealed that expression of the pro-apoptotic protein Bax, cytochrome c and caspase-3 was significantly diminished by 50 and 100 mg/kg Scutellaria baicalensis stem-leaf total flavonoid, while expression of the anti-apoptotic protein Bcl-2 was increased. Moreover, 100 mg/kg Scutellana baicalensis stem-leaf total flavonoid had a more dramatic effect than the lower dosage. These experimental findings indicate that Scutellaria baicalensis stem-leaf total flavonoid dose-dependently attenuates neuronal apoptosis induced by amyloid beta-peptide in the hippocampus, and it might mediate this by regulating the expression of Bax, cytochrome c, caspase-3 and Bcl-2.

Hydrogen sulfide protects against amyloid beta-peptide induced neuronal injury via attenuating inflammatory responses in a rat model

Neuroinflammation has been recognized to play a critical role in the pathogenesis of Alzheimer＇s disease （AD）, which is pathologically characterized by the accumulation of senile plaques containing activated microglia and amyloid β-peptides （Aβ）. In the present study, we examined the neuroprotective effects of hydrogen sulfide （H2S） on neuroinflammation in rats with Aβ1-40 hippocampal injection. We found that Aβ-induced rats exhibited a disorder of pyramidal cell layer arrangement, and a decrease of mean pyramidal cell number in the CA1 hippocampal region compared with those in sham operated rats. NaHS （a donor of H2S, 5.6 mg/kg/d, i.p.） treatment for 3 weeks rescued neuronal cell death significantly. Moreover, we found that H2S dramatically suppressed the release of TNF-α, IL-1β and IL-6 in the hippocampus. Consistently, both immunohistochemistry and Western blotting assays showed that H2S inhibited the upregulation of COX-2 and the activation of NF-κB in the hippocampus. In conclusion, our data indicate that H2S suppresses neuroinflammation via inhibition of the NF-κB activation pathway in the Aβ-induced rat model and has potential value for AD therapy.

Amyloid beta-peptide worsens cognitive impairment following cerebral ischemia-reperfusion injury

Amyloid 13-peptide, a major component of senile plaques in Alzheimer＇s disease, has been implicated in neuronal cell death and cognitive impairment. Recently, studies have shown that the pathogenesis of cerebral ischemia is closely linked with Alzheimer＇s disease. In this study, a rat model of global cerebral ischemia-reperfusion injury was established via occlusion of four arteries; meanwhile, fibrillar amyloid [3-peptide was injected into the rat lateral ventricle. The Morris water maze test and histological staining revealed that administration of amyloid 13-peptide could further aggravate impairments to learning and memory and neuronal cell death in the hippocampus of rats subjected to cerebral ischemia-reperfusion injury. Western blot showed that phosphorylation of tau protein and the activity of glycogen synthase kinase 313 were significantly stronger in cerebral ischemia-reperfusion injury rats subjected to amyloid [3-peptide administration than those undergo- ing cerebral ischemia-repetfusion or amyloid 13-peptide administration alone. Conversely, the activ- ity of protein phosphatase 2A was remarkably reduced in rats with cerebral ischemia-reperfusion injury following amyloid 13-peptide administration. These findings suggest that amyloid 13-peptide can potentiate tau phosphorylation induced by cerebral ischemia-reperfusion and thereby aggravate cognitive impairment.

Role of Notch-1 signaling pathway in PC12 cell apoptosis induced by amyloid beta-peptide(25–35)

Recent studies have demonstrated that Notch-1 expression is increased in the hippocampus of Alzheimer＇s disease patients. We speculate that Notch-1 signaling may be involved in PC12 cell apoptosis induced by amyloid beta-peptide （25-35） （Aβ25-35）. In the present study, PC12 cells were cultured with different doses （0, 0.1, 1.0, 10 and 100 nmol/L） of N-[N-（3,5-Difluorophenacetyl）-L-alanyl]-S-phenylglycine t-butyl ester, a Notch-1 signaling pathway inhibitor, for 30 minutes. Then cultured cells were induced with Aβ25-3s for 48 hours. Pretreatment of PC12 cells with high doses of N-[N-（3,5-Difluorophenacetyl）-L-alanyl]-S-phenylglycine t-butyl ester （〉 10 nmol/L） prolonged the survival of PC12 cells after Aβ25-35 induction, decreased the expression of apoptosis-related proteins caspase-3, -8, -9, increased the activity of oxidative stress-related superoxide dismutase and catalase, inhibited the production of active oxygen, and reduced nuclear factor kappa B expression. This study indicates that the Notch-1 signaling pathway plays a pivotal role in Aβ25-35-induced PC12 apoptosis.

Plasma amyloid-beta oligomer and phosphorylated tau:diagnostic tools for progressive Alzheimer's disease

Introduction:Spanning the three stages of the Alzheimer’s disease (AD) continuum,amyloid-beta(Aβ40and Aβ42) oligomers (AβO’s) and tau protein constitute a set of biomarkers ideally suited for the non-invasive monitoring of AD (Wolgin et al.,2022).AD progression is correlated with the presence of low molecular weight oligomers and not amyloid plaques.Moreover,low molecular weight AβO is present in the beginning and later stages of disease even when the plaque burden becomes prevalent.Furthermore.