Stages of granulovacuolar degeneration: their relation to Alzheimer’s disease and chronic stress response

被引:0
作者
Dietmar Rudolf Thal
Kelly Del Tredici
Albert C. Ludolph
Jeroen J. M. Hoozemans
Annemieke J. Rozemuller
Heiko Braak
Uwe Knippschild
机构
[1] University of Ulm,Laboratory of Neuropathology, Institute of Pathology, Center for Clinical Research
[2] University of Ulm,Department of Neurology
[3] VU University Medical Center,Department of Pathology
[4] University of Ulm,Department of General, Visceral, and Transplantation Surgery
来源
Acta Neuropathologica | 2011年 / 122卷
关键词
Granulovacuolar degeneration; Amyloid β-protein; Neurofibrillary tangles; τ-Protein; Dementia; Argyrophilic grain disease; Circadian clock; Chronic stress-response; pTDP43;
D O I
暂无
中图分类号
学科分类号
摘要
Granulovacuolar degeneration (GVD) is characterized by the presence of vacuolar cytoplasmic lesions in nerve cells of the medial temporal lobe. These changes occur in older non-diseased individuals as well as in patients with Alzheimer’s disease (AD), progressive supranuclear palsy (PSP), Pick’s, sporadic Parkinson’s (PD), and Guam diseases. We stained representative paraffin sections from all parts of the brain with anti-pTDP43, anti-CK1δ or anti-CK1ε from 14 non-demented elderly, 19 AD, 17 non-AD tauopathy, 9 sporadic PD, and 5 TDP43-proteinopathy [amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD)] cases. Our results showed five stages of GVD based on its distribution pattern: GVD began in the hippocampal subfields CA1, CA2, and the subiculum. In a second stage, entorhinal cortex, and CA4 neurons exhibited GVD. Additional neurons were involved in the temporal neocortex in stage 3, whereas the affection of the amygdala and/or the hypothalamus marked stage 4. A fifth and final stage was characterized by additional GVD in the cingulate cortex and occasionally in the frontal and parietal cortices as well as in the oral raphe and pedunculopontine tegmental nuclei. The GVD stages correlated with neurofibrillary tangle stages, Consortium to Establish a Registry for AD (CERAD) scores for neuritic plaque pathology, amyloid β-protein deposition phases, cerebral amyloid angiopathy stages, and clinical dementia rating (CDR) scores. No associations were seen between GVD stage and the presence of non-AD tauopathies, PD, ALS, or FTLD cases. In conclusion, GVD affects neurons in a hierarchical sequence that allows the distinction of five stages. The topographic distribution of GVD restricted to regions involved in response to chronic stress could indicate a link between GVD and chronically stressful influences. Moreover, the association of the GVD stages with those of AD-related pathology but not with other neurodegenerative disorders points to a possible role of GVD and the response to chronic stress in the pathogenesis of AD.
引用
收藏
页码:577 / 589
页数:12
相关论文
共 306 条
[1]  
Alafuzoff I(2009)Staging/typing of Lewy body related alpha-synuclein pathology: a study of the BrainNet Europe Consortium Acta Neuropathol 117 635-652
[2]  
Ince PG(1977)Neuronal loss, neurofibrillary tangles and granulovacuolar degeneration in the hippocampus with ageing and dementia. A quantitative study Acta Neuropathol (Berl) 37 111-118
[3]  
Arzberger T(1977)Granulovacuolar degeneration in the ageing brain and in dementia J Neuropathol Exp Neurol 36 474-487
[4]  
Al-Sarraj S(1980)Neurofibrillary tangles, granulovacuolar degeneration, and neuron loss in Down Syndrome: quantitative comparison with Alzheimer dementia Ann Neurol 7 462-465
[5]  
Bell J(2003)The locus coeruleus-noradrenergic system: modulation of behavioral state and state-dependent cognitive processes Brain Res Brain Res Rev 42 33-84
[6]  
Bodi I(2006)Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry Acta Neuropathol 112 389-404
[7]  
Bogdanovic N(1991)Demonstration of amyloid deposits and neurofibrillary changes in whole brain sections Brain Pathol 1 213-216
[8]  
Bugiani O(1991)Neuropathological stageing of Alzheimer-related changes Acta Neuropathol 82 239-259
[9]  
Ferrer I(2011)The pathological process underlying Alzheimer’s disease in individuals under thirty Acta Neuropathol 121 171-181
[10]  
Gelpi E(2003)Staging of brain pathology related to sporadic Parkinson’s disease Neurobiol Aging 24 197-211