Alzheimer disease

Nature Reviews Disease Primers, Год журнала: 2021, Номер 7(1)

Опубликована: Май 13, 2021

Язык: Английский

---

Hallmarks of neurodegenerative diseases

Cell, Год журнала: 2023, Номер 186(4), С. 693 - 714

Опубликована: Фев. 1, 2023

Summary

Decades of research have identified genetic factors and biochemical pathways involved in neurodegenerative diseases (NDDs). We present evidence for the following eight hallmarks NDD: pathological protein aggregation, synaptic neuronal network dysfunction, aberrant proteostasis, cytoskeletal abnormalities, altered energy homeostasis, DNA RNA defects, inflammation, cell death. describe hallmarks, their biomarkers, interactions as a framework to study NDDs using holistic approach. The can serve basis defining pathogenic mechanisms, categorizing different based on primary stratifying patients within specific NDD, designing multi-targeted, personalized therapies effectively halt NDDs.

Язык: Английский

---

Alzheimer’s disease: risk factors and potentially protective measures

Journal of Biomedical Science, Год журнала: 2019, Номер 26(1)

Опубликована: Май 9, 2019

Alzheimer’s disease (AD) is the most common type of dementia and typically manifests through a progressive loss episodic memory cognitive function, subsequently causing language visuospatial skills deficiencies, which are often accompanied by behavioral disorders such as apathy, aggressiveness depression. The presence extracellular plaques insoluble β-amyloid peptide (Aβ) neurofibrillary tangles (NFT) containing hyperphosphorylated tau protein (P-tau) in neuronal cytoplasm remarkable pathophysiological cause patients’ brains. Approximately 70% risk developing AD can be attributed to genetics. However, acquired factors cerebrovascular diseases, diabetes, hypertension, obesity dyslipidemia increase development. aim present minireview was summarize mechanism main for AD. As complement, some protective associated with lower incidence, reserve, physical activity diet will also addressed.

Язык: Английский

---

Practical considerations for choosing a mouse model of Alzheimer’s disease

Molecular Neurodegeneration, Год журнала: 2017, Номер 12(1)

Опубликована: Дек. 1, 2017

Alzheimer's disease (AD) is behaviorally identified by progressive memory impairment and pathologically characterized the triad of β-amyloid plaques, neurofibrillary tangles, neurodegeneration. Genetic mutations risk factors have been that are either causal or modify progression. These genetic pathological features serve as basis for creation validation mouse models AD. Efforts made in past quarter-century produced over 100 genetically engineered lines recapitulate some aspects AD clinicopathology. valuable resources understanding interactions contribute to cellular reactions engaged response. Here we focus on widely used stalwarts field recently developed bellwethers future. Rather than providing a summary each model, endeavor compare contrast approaches employed discuss their respective advantages limitations. We offer critical account variables which may inconsistent findings should be considered when choosing model interpreting results. hope present an insightful review current provide practical guide selecting best matched experimental question at hand.

Язык: Английский

---

Amyloid-β and tau complexity — towards improved biomarkers and targeted therapies

Nature Reviews Neurology, Год журнала: 2017, Номер 14(1), С. 22 - 39

Опубликована: Дек. 15, 2017

Язык: Английский

---

The role of innate immune responses and neuroinflammation in amyloid accumulation and progression of Alzheimer's disease

Immunology and Cell Biology, Год журнала: 2019, Номер 98(1), С. 28 - 41

Опубликована: Окт. 26, 2019

Abstract Alzheimer's disease ( AD ) is characterized by amyloid beta (Aβ) accumulation, tau pathology and neuroinflammation. Recently, there has been considerable interest in the role of neuroinflammation directly contributing to progression . Studies mice humans have identified a for microglial cells, resident innate immune cells central nervous system, Activated microglia are key hallmark secretion proinflammatory cytokines may result positive feedback loop between neurons microglia, resulting ongoing low‐grade inflammation. Traditionally, pathways Aβ production considered independently; however, recent studies suggest that these processes converge promote associated with Here we review importance inflammation development effects inflammatory responses on cellular neurons, including generation.

Язык: Английский

---

The physiological role of α‐synuclein and its relationship to Parkinson’s Disease

Journal of Neurochemistry, Год журнала: 2019, Номер 150(5), С. 475 - 486

Опубликована: Июль 3, 2019

Abstract The protein α‐synuclein has a central role in the pathogenesis of Parkinson’s disease (PD). In this review, we discuss recent results concerning its primary function, which appears to be on cell membranes. pre‐synaptic location synuclein suggested neurotransmitter release and it apparently associates with synaptic vesicles because their high curvature. Indeed, over‐expression inhibits vesicle exocytosis. However, loss not yet been shown have major effect transmission. Consistent work showing that can promote as well sense membrane curvature, analysis triple knockout mice now shows accelerates dilation exocytic fusion pore. This form regulation affects primarily slowly discharged lumenal cargo such neural peptides, but presumably also contributes maintenance site. image article is part Special Issue “Synuclein”.

Язык: Английский

---

Secreted amyloid-β precursor protein functions as a GABA _B R1a ligand to modulate synaptic transmission

Science, Год журнала: 2019, Номер 363(6423)

Опубликована: Янв. 11, 2019

A physiological function for sAPP? Although the pathological role of amyloid-β precursor protein (APP) in Alzheimer's disease is well studied, this has remained elusive. Rice et al. found that secreted ectodomain APP (sAPP) binds to GABA B R1a, metabotropic receptor inhibitory neurotransmitter γ-aminobutyric acid (GABA) (see Perspective by Korte). Binding suppressed synaptic vesicle release and modulated transmission plasticity mice. short, 17–amino peptide bound R1a's sushi 1 domain, conferring structure unstructured domain. Therapeutics targeting interaction could potentially benefit a range neurological disorders which signaling implicated. Science , issue p. eaao4827 ; see also 123

Язык: Английский

---

What Happens with the Circuit in Alzheimer's Disease in Mice and Humans?

Annual Review of Neuroscience, Год журнала: 2018, Номер 41(1), С. 277 - 297

Опубликована: Июль 8, 2018

A major mystery of many types neurological and psychiatric disorders, such as Alzheimer's disease (AD), remains the underlying, disease-specific neuronal damage. Because strong interconnectivity neurons in brain, dysfunction necessarily disrupts circuits. In this article, we review evidence for disruption large-scale networks from imaging studies humans relate it to cellular mouse models AD. The emerging picture is that some forms early network dysfunctions can be explained by excessively increased levels activity. notion hyperactivity receives support vivo vitro electrophysiological recordings mouse, which provide mechanistic insights underlying change excitability. Overall, key aspects AD-related mice are strikingly similar continuation a translational strategy.

Язык: Английский

---

Amyloid-beta peptide and tau protein crosstalk in Alzheimer’s disease

Neural Regeneration Research, Год журнала: 2021, Номер 17(8), С. 1666 - 1666

Опубликована: Дек. 10, 2021

Alzheimer's disease is a neurodegenerative that accounts for most of the 50-million dementia cases worldwide in 2018. A large amount evidence supports amyloid cascade hypothesis, which states amyloid-beta accumulation triggers tau hyperphosphorylation and aggregation form neurofibrillary tangles, these aggregates lead to inflammation, synaptic impairment, neuronal loss, thus cognitive decline behavioral abnormalities. The poor correlation found between plaques, have led scientific community question whether actually triggering neurodegeneration disease. occurrence tangles better correlates loss clinical symptoms and, although may initiate events, impairment likely effector molecule neurodegeneration. Recently, it has been shown cooperatively work impair transcription genes involved function more importantly, downregulation partially reverses transcriptional perturbations. Despite mounting points an interplay tau, some factors could independently affect both pathologies. Thus, dual pathway there are common upstream causing abnormalities proposed. Among others, immune system seems be strongly Other factors, as apolipoprotein E ε4 isoform suggested act link hyperphosphorylation. Interestingly, amyloid-beta-immunotherapy reduces not only but also levels animal models trials. Likewise, tau-immunotherapy levels. even though immunotherapy advanced than tau-immunotherapy, combined tau-directed therapies at early stages recently proposed strategy stop progression

Язык: Английский

---