CNS

Classical Disease Patterns Degenerative Inflammatory Neoplastic Blood

CNS Normal Pathology (13 Questions) Neurons Glia Astrocytes Oligodendrocytes Ependymal Cells Microglia Pathology (13 Questions) What is the fifth type of “glial” cell?

CNS DEGENERATIVE DISEASES CORTEX (dementias) BASAL GANGLIA and BRAIN STEM (parkinsonian) SPINOCEREBELLAR (ataxias) MOTOR NEURONS (muscle atrophy) Question #10 FOUR classical areas for brain degeneration, a decent anatomic classification.

CNS DEGENERATIVE DISEASES CORTEX (dementias) ALZHEIMER DISEASE Frontotemporal Pick Disease (also primarily frontal) Progressive Supranuclear Palsy (PSP) CorticoBasal Degeneration (CBD) Vascular Dementias (MID) ALZHEIMER disease is many times more common than all the other dementias put together, except for MID. Progressive supranuclear palsy (PSP) is a rare degenerative tauopathy involving the gradual deterioration and death of selected areas of the brain, chiefly basal ganglia and cortex. CBD is a similar tauopathy. Pick Disease is another tauopathy. Do you see a pattern here? Are “tau”-opathies (i.e., tau protein buildups) generally synonymous with CNS degenerative diseases? YES. CNS degenerative diseases were generally regarded as the same as “senility” until the PC police disallowed this word.

ALZHEIMER DISEASE CORTICAL (grey matter) ATROPHY Commonest cause of dementias (majority) Sporadic, 5-10% familial CORTICAL (grey matter) ATROPHY NEURITIC PLAQUES* (extraneuronal) NEUROFIBRILLARY TANGLES (intraneuronal) AMYLOID!!! (i.e., “BETA” amyloid) * NB: NOT at all like MS plaques.

Normal sulci.

Prominent sulci in cortical atrophy Prominent sulci in cortical atrophy. Why are the sulci, NOT the gyri, prominent in atrophy? Ans: cortical LOSS

Plaques and tangles and beta-amyloid of Alzheimer’s diaease

Neuritic plaques, stained with anti- beta amyloid immunostain Plaques and tangles and beta-amyloid Neuritic plaques Neuritic plaques, stained with anti- beta amyloid immunostain

Amyloid with congo red stain (LEFT), and Amyloid with congo red stain under polarization (RIGHT). Remember the amyloid of Alzheimer’s disease is BETA amyloid, NOT the usual kind of ALPHA amyloid seen with immunoglobulinproliferative diseases such as myelomas.

Neurons with tangles displacing nucleus, H & E

Neurons with TANGLES, often displacing NUCLEUS.

OTHER CORTICAL DEMENTIAS (tau gene/protein, tau-opathies) FRONTOTEMPORAL PICK DISEASE (LOBAR ATROPHY) PROGRESSIVE SUPRANUCLEAR PALSY (PSP) CORTICOBASAL DEGENERATION (CBD) VASCULAR DEMENTIA (MID) Tau is a gene, Tau protein is a microtubule protein associated with hyperphosphorylation in tau-opathies. MANY cortical dementias are TAU protein, and therefore most cortical dementias are known as TAUOPATHIES.

CNS DEGENERATIVE DISEASES BASAL GANGLIA and BRAIN STEM Parkinsonism Parkinson Disease Multiple System Atrophy Huntington Disease

Parkinsonism PARKINSON DISEASE Is a clinical “syndrome”, NOT a disease Diminished facial expression Stooped posture Slowness of voluntary movement “Festinating” gate (short, fast) Rigidity (cogwheel) “Pillrolling” tremor The above clinical findings involve pathology of the SUBSTANTIA NIGRA, and include: PARKINSON DISEASE MULTIPLE SYSTEM ATROPHY POSTENCEPHALIC PARKINSONISM Progr. Supranuc. Palsy, Cort. Basal Degen. (cortical disorders)

PALLOR of the SUBSTANTIA NIGRA (and LOCUS COERULEUS) PARKINSON DISEASE PALLOR of the SUBSTANTIA NIGRA (and LOCUS COERULEUS) LEWY BODIES (alpha-synuclein protein)

NORMALLY BLACK substantia nigra due to adequate dopamine.

PALE substantia nigra in Parkinson’s disease due to inadequate dopamine, normal on right.

Which patient has Parkinson’s disease. Ans: the RIGHT Why Which patient has Parkinson’s disease? Ans: the RIGHT Why? Ans: decreased dopamine

Lewy bodies are commonly regarded as diagnostic of Parkinson’s disease also. The main substance of the eosinophilic inclusion is alpha-synuclein.

主要内容 掌握神经系统的细胞及其基本病变； 掌握常见变性疾病的病理特点。 思考题： 1. Alzheimer病的病理特点？ 2. Parkinson病的病理特点？ 3. 脑组织中蛋白质异常聚集的机制有哪些？哪些疾病可能有蛋白质异常聚集？ 竺可青 病理学与法医学研究所 神经科学研究所 浙江大学医学院中国人脑库 zhukeqing@zju.edu.cn