ciało-człowieka: Amyloid

Evidence: 45 • authority: 92

Rodent Models of Alzheimer's Disease: Bridging the Translational Gap Through Systems-Level Integration.. Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder and a leading cause of dementia worldwide, yet effective disease-modifying therapies remain elusive. Rodent models have been indispensable for elucidating key pathological mechanisms, including amyloid-beta (Aβ) deposition, tau pathology, neuroinflammation, and synaptic dysfunction. However, despite decades of preclinical success, the translation of therapeutic findings from rodent studies to clinical efficacy in humans has been largely unsuccessful, highlighting critical limitations in current modelling approaches.…

Evidence: 100 • authority: 72

Amyloids are aggregates of proteins characterised by a fibrillar morphology of typically 7–13 nm in diameter, a β-sheet secondary structure (known as cross-β) and ability to be stained by particular dyes, such as Congo red. In the human body, amyloids have been linked to the development of various diseases. Pathogenic amyloids form when previously healthy proteins lose their normal structure and physiological functions (misfolding) and form fibrous deposits within and around cells. These protein misfolding and deposition processes disrupt the healthy function of tissues and organs. Such amyloids have been associated with (but not necessarily as the cause of) more than 50 human diseases, inc…

Evidence: 64 • authority: 92

Amyloid-β plaque diversity across brain regions in Alzheimer's disease and its relation to major clinicopathological traits.. Amyloid beta (Aβ) deposition and tau accumulation are neuropathological hallmarks of Alzheimer's disease (AD). While Aβ deposits present with a wide morphological variety, a comprehensive, cross-regional overview of Aβ plaque composition in AD and associations with clinicopathological traits are missing. In this study, we systematically documented the abundance and morphological diversity of Aβ plaques in up to 23 brain regions of 84 advanced AD cases. Deposits were segmented with a random forest pixel classifier in 4G8 diaminobenzidine stains and classified into six…

Evidence: 64 • authority: 90

Assessment of amyloid beta-protein precursor gene mutations in a large set of familial and sporadic Alzheimer disease cases.. A genetic locus associated with familial Alzheimer disease (FAD) and a candidate gene, APP, encoding the amyloid protein precursor have both been assigned previously to chromosome 21, and, in a few FAD families, mutations of APP have been detected. However, obligate crossovers between APP and FAD have also been reported in several FAD pedigrees, including FAD4, a large kindred showing highly suggestive evidence for linkage of the disorder to chromosome 21. In case the apparent APP crossover in FAD4 actually represented an intragenic recombination event or segregation…

Evidence: 54 • authority: 80

Deciphering the Morphological Difference of Amyloid Fibrils in Familial and Sporadic Alzheimers Diseases

Evidence: 54 • authority: 92

Prion Diseases-When Proteins Turn Lethal: Creutzfeldt-Jakob Disease (CJD) and the Quest for Classification, Diagnosis, Therapeutic Approaches, and Emerging Research.. Creutzfeldt-Jakob disease (CJD) is a rare and still fatal neurodegenerative disorder caused by prion protein misfolding in the central nervous system. Accumulation of the pathogenic isoform leads to neuronal damage, spongiform degeneration, and rapidly progressive dementia. The disease is divided into sporadic, familial, iatrogenic, and variant forms, with sporadic cases accounting for the majority of cases. Diagnosis remains challenging and relies on a combination of clinical assessment, neuroimaging, and laboratory biomarker…

Evidence: 54 • authority: 90

LR11/SorLA Expression Is Reduced in Sporadic Alzheimer Disease but not in Familial Alzheimer Disease. LR11 is an ApoE receptor that is enriched in the brain. We have shown that LR11 is markedly downregulated in patients with sporadic Alzheimer disease (AD). This finding led us to explore whether reduced LR11 expression reflects a primary mechanism of disease or merely a secondary consequence of other AD-associated changes. Therefore, LR11 expression was assessed in a transgenic mouse model of AD and familial AD (FAD) brains. Immunohistochemistry and immunoblotting of LR11 in PS1/APP transgenic and wild-type mice indicated that LR11 levels are not affected by genotype or accumulation of amyl…

Evidence: 54 • authority: 90

Genetics of familial and sporadic Alzheimer s disease. Alzheimer's disease (AD) is an age-related progressive neurodegenerative disorder. A majority of cases manifest as a late onset sporadic form but genetically the disease is divided into familial cases and sporadic cases. The familial form is due to mutations in three major genes (amyloid precursor protein (APP) gene, presenilin1 (PSEN1) gene and presenilin 2 (PSEN2) gene). In contrast, many genetic and environmental factors may contribute to determining the sporadic AD form. Despite many years of research and great progress in the knowledge of the molecular pathogenesis of AD, a full understanding of the etiology of the sporadic form is…

Evidence: 54 • authority: 80

Investigation of amyloid and microglial pathology in sporadic, familial and TREM2 variant Alzheimer's disease cases. Source: UCL Discovery (University College London). Year: 2017

Evidence: 54 • authority: 80

Protein kinase C and amyloid precursor protein processing in skin fibroblasts from sporadic and familial Alzheimer’s disease cases. Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. Year: 1999

Evidence: 54 • authority: 92

Protein-First, but Not Protein-Only: Rethinking Neurodegenerative Diseases Through Transgenic Mouse Models.. Neurodegenerative diseases represent a major and growing global health burden. Although these disorders are often clinically defined by symptoms and affected brain regions, many are mechanistically linked to abnormal protein accumulation, misfolding, impaired proteostasis, RNA dysregulation, mitochondrial dysfunction, and neuroinflammation. In this Perspective article, I discuss major neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies, multiple system atrophy, amyotrophic lateral sclerosis, frontotemporal dementia, Huntington's d…

Evidence: 54 • authority: 92

Synapse-associated neuropathological markers in Alzheimer's disease.. Abnormal amyloid-β and microtubule-associated protein are two intimately related proteinopathies central to the pathophysiology of Alzheimer's disease (AD). Both are often accompanied by cholesterol dysmetabolism and/or altered transport of this neutral lipid in carriers of APOEε4, a causal gene for early-onset (familial) Alzheimer's disease and the most important genetic risk factor for late-onset, also known as sporadic, Alzheimer's disease. Age, the principal risk factor for sporadic Alzheimer's disease, together with comorbidities such as cardiovascular diseases, diabetes and chronic inflammation, converge on synapses…