§5 alzheimer’s disease degenerative disease 选择性地累及某 1~2...
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§5 Alzheimer’s disease
•Degenerative disease选择性地累及某 1~2 个功能系统的神经细胞。•老年性痴呆临床表现: progressive dementiaCNS 功能的全面衰退,记忆和认知功能逐渐丧失,直至痴呆而死亡。 7~10 年以上。
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Alzheimer’s disease ( AD)
1907 AlÖis Alzheimer 报告: 51 岁,女性,多疑,记忆力障碍,时间、地点、定向力障碍,4 年半后死亡。
目前 西方: 5% 65 岁以上, 上海: 3% 65 岁以上, 4.69% 70岁以上
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Alzheimer’s disease
病 因 发 病 不明, 4 个 AD 相关基因 编码蛋白 基因定位APP gene amyloid -protein precursor 21q11.2-
21q22.1
ApoE 载脂蛋白 E 19q13-13.2
PS1 早老蛋白 1(Presinilin 1) 14q24.3
PS2 早老蛋白 2 1q31-42
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N 端 C 端
细胞外 细胞膜 细胞内
APP
非非 A A 生成途径生成途径
P3 P7
P3CT
A A 生成途径生成途径
A A P7 A4CT
APPs
APPAPP 水解及水解及 A A 生成模式生成模式图图
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Alzheimer’s disease
病 理 变 化肉眼 Brain atrophy组织学 Neurofibrillary tangles 神经原纤维缠结 Senile plaques 老年斑 Amyloid angiopathy 淀粉样血管病 Granulovacuolar degeneration 颗粒空泡 变性
Loss of neurons
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In this case of Alzheimer's disease, there is more marked atrophy seen superiorly and laterally, with sparing of the occipital region.
178
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神经原纤维缠
神经原纤维缠
结结This is a neurofibrillary "tangle" of Alzheimer's disease. The tangle appears as long pink filaments in the cytoplasm. They are composed of cytoskeletal intermediate filaments. 098
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Neurofibrillary changeNeurofibrillary change Ag impregnationAg impregnation
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Senile plaqueSenile plaque
The plaques of Alzheimer's disease are seen here with a silver stain. Such plaques are most numerous in the cerebral cortex and hippocampus. This dementia is marked mainly by progressive memory loss. 091
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• Primary intracranial tumor:
Glioma 胶质瘤( 40% ) Meningioma 脑膜瘤( 15% ) Acoustic neurinoma 听神经瘤( 8% ) Metastatic tumors: lung, breast
§6 Tumors分类发病率
children: glioma, medulloblastoma 髓母细胞瘤
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• Size, location > nature Local effect General effect
特点
影响
• Biologic ~ histologic malignancy• Invasion• Metastasis
tumor
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Differentiation 分化Clinical progression
Genetic changes
I. Astrocytoma 星形细胞瘤
Astrocytoma
Anaplastic astrocytoma间变性 -
Glioblastoma multiform
e
多形性胶质母细胞瘤
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atypia, mitotic rate,capillary, endothelial cells,necrosis, hemorrhage
AstrocytomaAnaplastic astrocytoma
Glioblastoma
multiforme
poorly definedgray-whitesolid
multiform 多形性 :cyst, necrosis, hemorrhage
Astrocytona
病变
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P53 mutation / loss of chr. 17pLoss of chr.22q
Rb mutation / loss of chr.13qP16 deletion / loss of chr.3pLoss of chr.19q
Loss of ch.10EGFR gene amplification
Genetic changes in astrocytomaNormal astrocyte
Astrocytoma
Anaplastic astrocytoma
Glioblaxtomamultiforme
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astrocytomaastrocytoma
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AstrocytomAstrocytoma a
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Glioblatona multiforme
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Giant cells in glioblastoma multiformeGiant cells in glioblastoma multiforme
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Giant cells in glioblastoma multiformGiant cells in glioblastoma multiformee
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Giant cells in glioblastoma Giant cells in glioblastoma multiforme, multiforme, IH GFAPIH GFAP
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Pseudopalisading (glioblastoma multiforme)Pseudopalisading (glioblastoma multiforme)
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Endothelial cell proliferation glioblastoma multiformEndothelial cell proliferation glioblastoma multiformee
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• < 20y• Cerebellum• Primitive undifferentiated cell• small tumor cells, scanty cytoplasm rosette 菊形团• Seeding through CSF • Highly malignant
II. Medulloblastoma 髓母细胞瘤
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Medulloblastoma Medulloblastoma
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Seeding of medulloblastoma
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• From : arachnoid cell 蛛网膜细胞• 部位 : ~ arachnoid granulation• dura 硬脑膜• 大体: solid, gritty 砂粒样• 光镜: whorl-like pattern• psammoma 砂粒体• Malignant: rare
III. Meningioma 脑膜瘤
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meningiomameningioma
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Here is another benign meningioma beneath the dura. These neoplasms are slow growing, but may reach a large size before symptoms lead to detection.
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Meningioma of sphenoid wingMeningioma of sphenoid wing
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• From: Schwann cell• 大体 : encapsulated, solitary ~ nerves, spinal roots• 光镜 : Spindle tumor cells, 排列成 束状,网状• Benign
IV. Neurilemmoma 神经鞘瘤 Schwannoma
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Acoustic schwannomaAcoustic schwannoma
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Schwannoma of a spinal root Schwannoma of a spinal root
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Acoustic schwannomaAcoustic schwannoma
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Gemistocytix astrocytomaGemistocytix astrocytoma
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Gemistocytix astrocytomaGemistocytix astrocytoma
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SchwannomaSchwannoma
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Inflammation Tumor Trauma… ...
Edema
Hydrocephalus
IIPherniation