Cellular, synaptic, and biochemical features of resilient cognition in Alzheimer's disease

被引:81
作者
Arnold, Steven E. [1 ,2 ]
Louneva, Natalia
Cao, Kajia [3 ]
Wang, Li-San [3 ]
Han, Li-Ying
Wolk, David A. [2 ]
Negash, Selamawit
Leurgans, Sue E. [4 ]
Schneider, Julie A. [4 ]
Buchman, Aron S. [4 ]
Wilson, Robert S. [4 ]
Bennett, David A. [4 ]
机构
[1] Univ Penn, Penn Memory Ctr, Dept Psychiat, Philadelphia, PA 19104 USA
[2] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA
[3] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA
[4] Rush Univ, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA
基金
美国国家卫生研究院;
关键词
Cognitive reserve; Synapse; Synaptophysin; Synaptopodin; Glial fibrillary acidic protein; Antibody microarray; AMYLOID LOAD; NEUROFIBRILLARY TANGLES; NEURONAL HYPERTROPHY; CLINICAL-DIAGNOSIS; NEUROPATHOLOGY; IMPAIRMENT; EXPRESSION; DEMENTIA; PLAQUES; CORTEX;
D O I
10.1016/j.neurobiolaging.2012.03.004
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
Although neuritic plaques and neurofibrillary tangles in older adults are correlated with cognitive impairment and severity of dementia, it has long been recognized that the relationship is imperfect, as some people exhibit normal cognition despite high levels of Alzheimer's disease (AD) pathology. We compared the cellular, synaptic, and biochemical composition of midfrontal cortices in female subjects from the Religious Orders Study who were stratified into three subgroups: (1) pathological AD with normal cognition ("AD-Resilient"), (2) pathological AD with AD-typical dementia ("AD-Dementia"), and (3) pathologically normal with normal cognition ("Normal Comparison"). The AD-Resilient group exhibited preserved densities of synaptophysin-labeled presynaptic terminals and synaptopodin-labeled dendritic spines compared with the AD-Dementia group, and increased densities of glial fibrillary acidic protein astrocytes compared with both the AD-Dementia and Normal Comparison groups. Further, in a discovery-type antibody microarray protein analysis, we identified a number of candidate protein abnormalities that were associated with a particular diagnostic group. These data characterize cellular and synaptic features and identify novel biochemical targets that may be associated with resilient cognitive brain aging in the setting of pathological AD. (C) 2013 Elsevier Inc. All rights reserved.
引用
收藏
页码:157 / 168
页数:12
相关论文
共 60 条
[1]   Anatomical and physiological plasticity of dendritic spines [J].
Alvarez, Veronica A. ;
Sabatini, Bernardo L. .
ANNUAL REVIEW OF NEUROSCIENCE, 2007, 30 :79-97
[2]   Protein expression changes in spinal muscular atrophy revealed with a novel antibody array technology [J].
Anderson, K ;
Potter, A ;
Baban, D ;
Davies, KE .
BRAIN, 2003, 126 :2052-2064
[3]  
[Anonymous], 2000, FORCE DSM 4 DSM 4 T, DOI 10.1176/dsm10.1176/appi.books.9780890420249.dsm-iv-tr
[4]   Synaptic degeneration in Alzheimer's disease [J].
Arendt, Thomas .
ACTA NEUROPATHOLOGICA, 2009, 118 (01) :167-179
[5]   The Topographical and Neuroanatomical Distribution of Neurofibrillary Tangles and Neuritic Plaques in the Cerebral Cortex of Patients with Alzheimer's Disease [J].
Arnold, Steven E. ;
Hyman, Bradley T. ;
Flory, Jill ;
Damasio, Antonio R. ;
Van Hoesen, Gary W. .
CEREBRAL CORTEX, 1991, 1 (01) :103-116
[6]   Microinfarct Pathology, Dementia, and Cognitive Systems [J].
Arvanitakis, Zoe ;
Leurgans, Sue E. ;
Barnes, Lisa L. ;
Bennett, David A. ;
Schneider, Julie A. .
STROKE, 2011, 42 (03) :722-727
[7]   Dendritic pathology in Alzheimer's disease [J].
Baloyannis, S. J. .
JOURNAL OF THE NEUROLOGICAL SCIENCES, 2009, 283 (1-2) :153-157
[8]   The cholinergic deficit coincides with Aβ deposition at the earliest histopathologic stages of Alzheimer disease [J].
Beach, TG ;
Kuo, YM ;
Spiegel, K ;
Emmerling, MR ;
Sue, LI ;
Kokjohn, K ;
Roher, AE .
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 2000, 59 (04) :308-313
[9]  
Bennett D. A., 2002, Neurology, V59, P198
[10]   Neuropathology of older persons without cognitive impairment from two community-based studies [J].
Bennett, D. A. ;
Schneider, J. A. ;
Arvanitakis, Z. ;
Kelly, J. F. ;
Aggarwal, N. T. ;
Shah, R. C. ;
Wilson, R. S. .
NEUROLOGY, 2006, 66 (12) :1837-1844