老年人大脑蛋白质组的公正分类解决了认知障碍的不同临床和病理生理学亚型
Lenora Higginbotham1, E Kathleen Carter2, Eric B Dammer3
1Goizueta Alzheimer's Disease Research Center, Emory University School of Medicine, Atlanta, GA, USA; Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA.
Neurobiology of disease
|September 9, 2023
概括
这项研究揭示了认知障碍中的不同分子亚型,确定了具有非典型阿尔茨海默病 (AD) 标志甚至认知性的群体. 这些发现提高了对大脑衰老和神经退行性疾病异质性的理解.
科学领域:
- 神经科学是一个神经科学.
- 蛋白质组学是指蛋白质组学.
- 老年学是指老年学的学科.
背景情况:
- 老年人的认知障碍具有复杂的分子基础,超出了传统的疾病标志物.
- 分子亚型对理解认知衰退的生物异质性至关重要.
研究的目的:
- 通过蛋白质基因分析来解决认知障碍的生物学异质性.
- 在轻度认知障碍 (MCI) 和阿尔茨海默氏症 (AD) 痴呆病例中识别不同的分子亚型.
主要方法:
- 使用定量质谱法测量了600多个背侧前额皮层组织样本中的大约8000种蛋白质.
- 对MCI和AD病例进行了基于个体蛋白质组特征的公正分类.
主要成果:
- 在MCI和AD病例中确定了三个不同的分子类,显示出不同的细胞类型和生物本体表达.
- 两类人表现出不典型的分子特征,包括突触标记升高和炎症标记降低,与典型的AD神经退行形成鲜明对比.
- 一个具有非典型特征的类与认知性有关,展示了性的标志.
结论:
- 蛋白质组亚型有效地解决了认知障碍中的分子异质性.
- 已识别的亚型有可能提高神经退行性疾病的诊断和治疗精度.
- 这些发现突显了大脑衰老的复杂性,并表明了通往认知性的途径.
相关概念视频
Amyloid Fibrils
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, normally used to...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
Amyloid Fibrils
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, normally used to...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
Alzheimer's Disease: Overview
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 and tau...
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ and tau...
Prosopagnosia
Prosopagnosia, also known as face blindness, is the inability to recognize faces. In severe cases, individuals with prosopagnosia may not recognize close family members, including parents and spouses, by their faces. For instance, someone with prosopagnosia might walk past their child in a crowd, only realizing their mistake upon noticing their child's distinctive backpack or favorite jacket. Prosopagnosia specifically impairs facial recognition, while the recognition of other objects or...
Alzheimer Disease l: Introduction
Alzheimer disease is a chronic, progressive, and irreversible neurodegenerative disorder and the most common cause of dementia in older adults. It leads to gradual neuronal loss, causing cognitive decline, behavioral changes, and loss of functional independence.Risk Factors and EtiologyThe disease is multifactorial. Age is the strongest risk factor, with prevalence doubling every 5 years after age 65. Genetic factors include mutations in genes such as APP, PSEN1, and PSEN2, which are associated...
Alzheimer Disease ll: Pathophysiology
Alzheimer disease involves structural changes in the brain that begin long before symptoms appear. The most distinctive features are extracellular neuritic plaques and intracellular neurofibrillary tangles.Neuritic plaques form in the cerebral cortex and around blood vessels. These plaques contain a dense core of beta-amyloid (Aβ)—a toxic protein fragment that clumps outside neurons. The core is surrounded by damaged neuronal extensions, as well as reactive astrocytes and microglia. Abnormal...


