§5 alzheimer’s disease degenerative disease 选择性地累及某 1~2...

§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。

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

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

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

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

In this case of Alzheimer's disease, there is more marked atrophy seen superiorly and laterally, with sparing of the occipital region.

178

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

Neurofibrillary changeNeurofibrillary change Ag impregnationAg impregnation

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

• 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

• Size, location > nature Local effect General effect

特点

影响

• Biologic ~ histologic malignancy• Invasion• Metastasis

tumor

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

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

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

astrocytomaastrocytoma

AstrocytomAstrocytoma a

Glioblatona multiforme

Giant cells in glioblastoma multiformeGiant cells in glioblastoma multiforme

Giant cells in glioblastoma multiformGiant cells in glioblastoma multiformee

Giant cells in glioblastoma Giant cells in glioblastoma multiforme, multiforme, IH GFAPIH GFAP

Pseudopalisading (glioblastoma multiforme)Pseudopalisading (glioblastoma multiforme)

Endothelial cell proliferation glioblastoma multiformEndothelial cell proliferation glioblastoma multiformee

• < 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

Medulloblastoma Medulloblastoma

Seeding of medulloblastoma

• 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

meningiomameningioma

Here is another benign meningioma beneath the dura. These neoplasms are slow growing, but may reach a large size before symptoms lead to detection.

Meningioma of sphenoid wingMeningioma of sphenoid wing

• 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

Acoustic schwannomaAcoustic schwannoma

Schwannoma of a spinal root Schwannoma of a spinal root

Acoustic schwannomaAcoustic schwannoma

Gemistocytix astrocytomaGemistocytix astrocytoma

Gemistocytix astrocytomaGemistocytix astrocytoma

SchwannomaSchwannoma

Inflammation Tumor Trauma… ...

Edema

Hydrocephalus

IIPherniation