多重系统缩与粉样蛋白-β主导的阿尔茨海默病神经病理变化
Tomoya Kon1,2, Shojiro Ichimata1,3, Daniel G Di Luca4,5
1Tanz Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, ON M5T 0S8, Canada.
Brain communications
|May 7, 2024
概括
这项研究确定了一种罕见的多重系统缩 (MSA) 变异,同时出现了粉样β和α-synuclein病理. 这种混合病理,称为amyloid-β-predominant阿尔茨海默氏症神经病理变化-MSA,可能会影响神经退行性疾病的治疗策略.
科学领域:
- 神经病理学神经病理学
- 神经退行性疾病 神经退行性疾病
- 蛋白质错折叠疾病 蛋白质错折叠疾病
背景情况:
- 多个系统缩 (MSA) 的特点是α-synuclein病理.
- 在MSA中,混合病理不常见,通常涉及病或阿尔茨海默氏病变化.
- 在同一大脑区域同时存在不同的错误折叠蛋白质在MSA中被认为是罕见的.
研究的目的:
- 为了研究一种罕见的MSA变体与同时存在的粉样β和α-synuclein病理.
- 描述这些混合病理病例的神经病理和遗传特征.
- 了解MSA对诊断和治疗策略的影响.
主要方法:
- 对21例MSA病例的神经病理学评估,确定了4例高粉样β和低tau病理.
- 绘制α-synuclein病理和测量质细胞质内含的测量.
- 在MSA和阿尔茨海默病 (AD) 病例中比较粉样β.
- α-Synuclein播种试验和遗传检测 (APOE,MAPT,PSEN1,PSEN2,APP) 的使用.
主要成果:
- 确定了四例MSA与粉样β主导阿尔茨海默氏症神经病理变化的病例.
- 这些病例与典型的MSA相比,没有明显的临床或MRI概况.
- 所有测试的病例都携带APOE ɛ4等位基因;粉样β分析显示斑块形成的时间比AD.
- 神经元损失和α-synuclein病理严重程度与典型的MSA相比.
结论:
- 一种罕见的混合病理变体MSA,粉样β主导的阿尔茨海默氏症神经病理变化-MSA,存在与重叠的粉样β和α-synuclein.
- 这种变异可能不会改变预后,但可能会影响α-synuclein向疗法的疗效.
- 临床医生应该意识到这种变异,因为生物标志物变得越来越普遍,考虑到治疗反应的区域蛋白重叠.
相关概念视频
01:26Alzheimer's Disease: Overview
467
Alzheimer's Disease (AD) is a continually advancing neurodegenerative disorder, distinguished by escalating memory loss, cognitive dysfunction, and dementia. The disease unfolds in three stages: preclinical, mild cognitive impairment (MCI), and dementia. Its onset is insidious, and the progression gradual, with the cause not well explained by other disorders.
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ...
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ...
467
03:03Amyloid Fibrils
9.5K
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
9.5K
01:22Alzheimer's Disease: Treatment
181
Alzheimer's Disease (AD), a neurodegenerative disorder, is pathologically identified by amyloid plaques and neurofibrillary tangles composed of tau protein. AD pharmacotherapy aims to manage cognitive symptoms, delay disease progression, and treat behavioral symptoms. The treatment is primarily symptomatic and palliative, with no definitive disease-modifying therapy available. Cholinesterase inhibitors, including donepezil (Aricept), rivastigmine (Exelon), and galantamine (Razadyne), are...
181
01:15Parkinson's Disease: Overview
533
Neurodegenerative disorders are progressive diseases that cause irreversible damage and loss to neurons in specific brain areas. Examples of these disorders include Parkinson's disease, Alzheimer's disease, Multiple Sclerosis (MS), and Amyotrophic Lateral Sclerosis (ALS). These disorders share characteristics such as proteinopathies, selective neuronal vulnerability, and a complex interplay between genetic and environmental factors. The primary therapeutic goal for these conditions is...
533
01:37Neural Regulation
39.4K
Digestion begins with a cephalic phase that prepares the digestive system to receive food. When our brain processes visual or olfactory information about food, it triggers impulses in the cranial nerves innervating the salivary glands and stomach to prepare for food.
39.4K