Biochemical assessment of precuneus and posterior cingulate gyrus in the context of brain aging and Alzheimer's disease.
Biochemical assessment of precuneus and posterior cingulate gyrus in the context of brain aging and Alzheimer's disease.
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DOI：
10.1371/journal.pone.0105784
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Roher AE
中科院分区：
文献类型：
--
作者：
Maarouf CL;Kokjohn TA;Walker DG;Whiteside CM;Kalback WM;Whetzel A;Sue LI;Serrano G;Jacobson SA;Sabbagh MN;Reiman EM;Beach TG;Roher AE
确定大脑在“正常”衰老过程中发生的生化变化，是了解神经退行性疾病的病理生理学以及区分病理条件和衰老相关变化的重要组成部分。根据年龄和没有神经或重大神经退行性疾病的证据选择了三组：1)青壮年个体，平均年龄26岁(n = 9)；2)中年受试者，平均年龄59岁(n = 5)；3)高龄个体，平均年龄93岁(n = 6)。使用ELISA和Western blotting方法，我们量化并比较了与神经退行性疾病相关的几个关键分子在楔前和扣带后回的水平，这两个大脑区域在阿尔茨海默病的过程中显示出早期的影像变化。我们的实验表明，随着年龄的增长，新出现的大脑病理的生物指标保持稳定或下降。一个例外是S100B，随着年龄的增长，S100B的含量显著增加。在衰老过程中，神经纤维缠结沉积增加，即使在没有淀粉样沉积的情况下也是如此，这表明淀粉样斑块的存在不是其发展的必要条件，有限的缠结密度是正常衰老的一部分。我们的研究补充了先前对老年受试者神经病理学的评估，在目前参与研究的少数人的限制下，它为在衰老和痴呆过程中观察到的分子和结构异质性增加了有价值的信息。这项工作强调了需要通过直接观察来检查淀粉样蛋白沉积过程是如何在痴呆症出现的最早阶段之前展开或变化的。
Defining the biochemical alterations that occur in the brain during “normal” aging is an important part of understanding the pathophysiology of neurodegenerative diseases and of distinguishing pathological conditions from aging-associated changes. Three groups were selected based on age and on having no evidence of neurological or significant neurodegenerative disease: 1) young adult individuals, average age 26 years (n = 9); 2) middle-aged subjects, average age 59 years (n = 5); 3) oldest-old individuals, average age 93 years (n = 6). Using ELISA and Western blotting methods, we quantified and compared the levels of several key molecules associated with neurodegenerative disease in the precuneus and posterior cingulate gyrus, two brain regions known to exhibit early imaging alterations during the course of Alzheimer’s disease. Our experiments revealed that the bioindicators of emerging brain pathology remained steady or decreased with advancing age. One exception was S100B, which significantly increased with age. Along the process of aging, neurofibrillary tangle deposition increased, even in the absence of amyloid deposition, suggesting the presence of amyloid plaques is not obligatory for their development and that limited tangle density is a part of normal aging. Our study complements a previous assessment of neuropathology in oldest-old subjects, and within the limitations of the small number of individuals involved in the present investigation, it adds valuable information to the molecular and structural heterogeneity observed along the course of aging and dementia. This work underscores the need to examine through direct observation how the processes of amyloid deposition unfold or change prior to the earliest phases of dementia emergence.
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影响因子：
12.7
作者：
Ahlgren, S;Li, GL;Olsson, Y
通讯作者：
Olsson, Y
DOI：
10.2174/1568013033358635
发表时间：
2003-03-01
期刊：
Current Medicinal Chemistry - Immunology Endocrine & Metabolic Agents
影响因子：
--
作者：
Beach, T. G.;Walker, D. G.;Roher, A. E.
通讯作者：
Roher, A. E.
影响因子：
4.2
作者：
Bartzokis G
通讯作者：
Bartzokis G
影响因子：
9.9
作者：
Chhatwal, Jasmeer P.;Schultz, Aaron P.;Sperling, Reisa A.
通讯作者：
Sperling, Reisa A.
影响因子：
6.2
作者：
BEACH, TG;WALKER, R;MCGEER, EG
通讯作者：
MCGEER, EG