A quantitative study of α-synuclein pathology in fifteen cases of dementia associated with Parkinson disease

被引:38
作者
Armstrong, Richard A. [1 ]
Kotzbauer, Paul T. [2 ,3 ,4 ]
Perlmutter, Joel S. [2 ,4 ,5 ,6 ,7 ,8 ]
Campbell, Meghan C. [2 ,5 ]
Hurth, Kyle M. [9 ]
Schmidt, Robert E. [9 ]
Cairns, Nigel J. [2 ,4 ,9 ,10 ]
机构
[1] Aston Univ, Birmingham B4 7ET, W Midlands, England
[2] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA
[3] Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO USA
[4] Washington Univ, Sch Med, Hope Ctr Neurol Disorders, St Louis, MO USA
[5] Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA
[6] Washington Univ, Sch Med, Dept Anat & Neurobiol, St Louis, MO 63110 USA
[7] Washington Univ, Sch Med, Program Occupat Therapy, St Louis, MO USA
[8] Washington Univ, Sch Med, Program Phys Therapy, St Louis, MO USA
[9] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA
[10] Washington Univ, Sch Med, Knight Alzheimers Dis Res Ctr, St Louis, MO USA
基金
美国国家卫生研究院;
关键词
Parkinson disease with dementia (DPD); alpha-Synuclein; Lewy bodies (LB); Lewy neurites (LN); Lewy grains (LG); Principal components analysis (PCA); ARGYROPHILIC GRAIN DISEASE; CREUTZFELDT-JAKOB-DISEASE; ALZHEIMERS-DISEASE; LEWY BODIES; DIAGNOSIS; CONSORTIUM; INCLUSIONS; DISORDERS; FREQUENCY; DEPOSITS;
D O I
10.1007/s00702-013-1084-z
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
The alpha-synuclein-immunoreactive pathology of dementia associated with Parkinson disease (DPD) comprises Lewy bodies (LB), Lewy neurites (LN), and Lewy grains (LG). The densities of LB, LN, LG together with vacuoles, neurons, abnormally enlarged neurons (EN), and glial cell nuclei were measured in fifteen cases of DPD. Densities of LN and LG were up to 19 and 70 times those of LB, respectively, depending on region. Densities were significantly greater in amygdala, entorhinal cortex (EC), and sectors CA2/CA3 of the hippocampus, whereas middle frontal gyrus, sector CA1, and dentate gyrus were least affected. Low densities of vacuoles and EN were recorded in most regions. There were differences in the numerical density of neurons between regions, but no statistical difference between patients and controls. In the cortex, the density of LB and vacuoles was similar in upper and lower laminae, while the densities of LN and LG were greater in upper cortex. The densities of LB, LN, and LG were positively correlated. Principal components analysis suggested that DPD cases were heterogeneous with pathology primarily affecting either hippocampus or cortex. The data suggest in DPD: (1) ratio of LN and LG to LB varies between regions, (2) low densities of vacuoles and EN are present in most brain regions, (3) degeneration occurs across cortical laminae, upper laminae being particularly affected, (4) LB, LN and LG may represent degeneration of the same neurons, and (5) disease heterogeneity may result from variation in anatomical pathway affected by cell-to-cell transfer of alpha-synuclein.
引用
收藏
页码:171 / 181
页数:11
相关论文
共 40 条
[1]  
[Anonymous], 1980, STAT METHODS
[2]  
Antal A, 1998, CLIN NEUROSCI, V5, P147
[3]   A quantitative study of the pathological changes in the cerebellum in 15 cases of variant Creutzfeldt-Jakob disease (vCJD) [J].
Armstrong, R. A. ;
Ironside, J. W. ;
Lantos, P. L. ;
Cairns, N. J. .
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, 2009, 35 (01) :36-45
[4]  
Armstrong RA, 1998, ALZHEIMERS REP, V1, P159
[5]   Quantifying the pathology of neurodegenerative disorders: quantitative measurements, sampling strategies and data analysis [J].
Armstrong, RA .
HISTOPATHOLOGY, 2003, 42 (06) :521-529
[6]   Spatial correlations between the vacuolation, prion protein deposits, and surviving neurons in the cerebral cortex in sporadic Creutzfeldt-Jakob disease [J].
Armstrong, RA ;
Lantos, PL ;
Cairns, NJ .
NEUROPATHOLOGY, 2001, 21 (04) :266-271
[7]   Correlations between the morphology of diffuse and primitive beta-amyloid (A beta) deposits and the frequency of associated cells in Down's syndrome [J].
Armstrong, RA .
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, 1996, 22 (06) :527-530
[8]  
Armstrong RA, 1997, NEUROSCI RES COMMUN, V21, P145
[9]   Visual signs and symptoms of Parkinson's disease [J].
Armstrong, Richard A. .
CLINICAL AND EXPERIMENTAL OPTOMETRY, 2008, 91 (02) :129-138
[10]   Different molecular pathologies result in similar spatial patterns of cellular inclusions in neurodegenerative disease: a comparative study of eight disorders [J].
Armstrong, Richard A. ;
Cairns, Nigel J. .
JOURNAL OF NEURAL TRANSMISSION, 2012, 119 (12) :1551-1560