9 neuropathology lecture 3: neurodegenerative diseases

Question 1

T/F- those diseases that affect primarily neurons of the cerebral cortex result in dementia with very little movement disorder, while those affecting primarily neurons of the cerebellum, brainstem, or spinal cord result in movement and/or autonomic disorders with very little dementia.

Answer 1

true

Question 2

Name 3 degenerative diseases affecting the cerebral cortex

Answer 2

Alzheimers
Pick’s disease
Dementia with Lewy Bodies

Question 3

Name 4 degenerative diseases affecting the basal ganglia and brainstem

Answer 3

• Parkinsons disesease
• Multiple system atrophy
• Progressive supranuclear palsy
• Huntington’s disease

Question 4

Name 1 category of degenerative disease affecting the spinocerebellar tracts

Answer 4

spinocerebellar ataxias

Question 5

Name one degenerative disease affecting motor neurons

Answer 5

amyotrophic lateral sclerosis

Question 6

Define dementia

Answer 6

acquired, cognitive impairments in an alert individual that are sufficiently severe to affect occupational and/or social functioning

Question 7

Pure alzheimer’s accounts for ___% of all dementias

Answer 7

40

Question 8

Alzheimer’s affects ___% of individuals over 65 and ___% of individuals over 85

Answer 8

5%

50%

Question 9

T/F- the majority of cases of alzheimer’s disease are familial

Answer 9

False, only 5-10% are familial

Question 10

How is alzheimer’s diagnosed?

Answer 10

• Clinical dementia with relatively specific, testable cognitive abnormalities
• Absence of other forms of organic dementia (tumors, infarcts, etc.)
• Imaging studies to show cortical atrophy
• Autopsy confirmation of appropriate histopathology

Question 11

Grossly, in alzheimers what will you see?

Answer 11

cortical atrophy

Question 12

What will histopathology show for alzheimers?

Answer 12

− Neuritic plaques

− Neurofibrillary tangles −Amyloid angiopathy

Question 13

Neuritic plaques (senile plaques) are a deposition of amyloid (product of amyloid precursor protein) which result in local injury to neuronal processes. What are attempts at repair called?

Answer 13

“sprouting”

Question 14

T/F- neuritic plaques have a close association with cerebral capillaries

Answer 14

true

Question 15

T/F- amyloid precursor protein is a selectively expressed transmembrane protein

Answer 15

False it is ubiquitously expressed transmembrane proteins:

Question 16

neurofibrilary tangles are ____philic

Answer 16

argyrophilic (silver stain)

Question 17

What gene encodes tau?

Answer 17

17q21 (6 isoforms in the CNS)

Question 18

Where in a neuron is tau located?

Answer 18

predominantly in axons

Question 19

What does tau do?

Answer 19

promotes microtubule polymerization and stabilization

Question 20

T/F- the tau in neurofibrillary tangles is abnormally phosphorylated

Answer 20

true

Question 21

What will gross image of pick’s disease brain show?

Answer 21

cortical atrophy

Question 22

What will histopathology of Pick’s disease show?

Answer 22

• Pick bodies – tau containing intraneuronal inclusion bodies
• Neurofibrillary tangles - also contain tau, but filaments are not
paired helical filaments
• No neuritic plaques or amyloid angiopathy

Question 23

Pick’s disease affects the _____lobe primarily and spares the_______

Answer 23

frontal lobe most affected

sparing of the posterior superior tempral gyrus

Question 24

What pathway is damaged in parkinsons?

Answer 24

Nigrostriatal dopaminergic system

Question 25

Name 3 symptoms of parkinson disease

Answer 25

– Tremor – Loss of spontaneous movement – Rigidity

Question 26

Parkinson disease is the most common underlying cause of parkinsonism. What are other possibilites?

Answer 26

– Multiple system degenerations – Progressive supranuclear palsy – Drugs – e.g. haloperidol, methotrexate – Toxins – MPTP (a contaminate of meperidine, aka Demerol)

Question 27

What age is the peak incidence of parkinson disease?

Answer 27

55-65 years

Question 28

Are familial forms of parkinsons common?

Answer 28

No, its rare

Question 29

Familial parkinson disease involves the _____ and _____ genes

Answer 29

alpha-synuclein | parkin

Question 30

Name 2 histologic characteristics of parkinsons disease

Answer 30

– Loss of pigmented neurons in substantia nigra | – Lewy bodies

Question 31

What is a lewy body?

Answer 31

Intraneuronal cytoplasmic inclusions

Question 32

T/F- in parkinson's disease you'll also likely see focal deposits of extracellular pigment

Answer 32

true

Question 33

What is the definition of dementia with Lewy Bodies (DLB)

Answer 33

A progressive dementia syndrome in the elderly with fluctuating cognition associated with Parkinsonism

Question 34

What pathologic features are characteristic of dementia with lewy bodies?

Answer 34

– Cortical atrophy (mild-to-moderate) – Cortical Lewy bodies – Lewy-related neurites -Neuritic plaques & neurofibrillary tangles(not essential to diagnosis)

Question 35

What pathologic features are characteristic of dementia with lewy bodies?

Answer 35

– Cortical atrophy (mild-to-moderate) – Cortical Lewy bodies – Lewy-related neurites -Neuritic plaques & neurofibrillary tangles(not essential to diagnosis)

Question 36

T/F- in DLB you will likely see mild frontal atrophy and pallor of the substantial nigra

Answer 36

true

Question 37

What is the term for A group of neurodegenerative disorders characterized by α- synuclein positive glial cytoplasmic inclusions (usually oligodendrocytes)

Answer 37

multiple system atrophy (MSA)

Question 38

What is the term for A group of neurodegenerative disorders characterized by α- synuclein positive glial cytoplasmic inclusions (usually oligodendrocytes)

Answer 38

multiple system atrophy (MSA)

Question 39

Name the 3 recognized forms of multiple system atrophy

Answer 39

striatonigral degeneration olivopontocerebellar atrophy Shy-Drager syndrome

Question 40

Which form of MSA is predominated by parkinsonism?

Answer 40

striatonigral degeneration

Question 41

Which form of MSA is predominated by cerebellar signs?

Answer 41

olivopontocerebrellar atrophy

Question 42

Which form of MSA is predominated by autonomic failure?

Answer 42

shy-drager syndrome

Question 43

What is the thing that links the clinically desperate syndromes of MSA together?

Answer 43

glial inclusions

Question 44

T/F- glial inclusions are limited to sporadic forms of OPCA (olivopontocerebrellar atrophy) and are not found in hereditary forms

Answer 44

true

Question 45

Progressive supranuclear palsy will show atrophy of the ______ , _____, and _____ and depigmentation of the _______

Answer 45

basal ganglia midbrain pons substantia nigra

Question 46

Histopathology of supra nuclear palsy will show intraneuronal globoid neurofibrillary tangles in the _____ and _______ and cytoplasmic accumulation of ____ in neurons and glial cells

Answer 46

brainstem and basal ganglia | tau

Question 47

What is critical to making the diagnosis in progressive supra nuclear palsy?

Answer 47

Globoid NFTs in basal ganglia and brainstem

Question 48

CAG codes for what?

Answer 48

polyglutamine

Question 49

Huntington's disease mode of inheritance? trinucleotide repeat?

Answer 49

AD | CAG repeat

Question 50

Spinocerebrellar ataxias: mode of inheritance? trinucleotide repeat?

Answer 50

AD or AR | CAG repeat

Question 51

Friedeich's ataxia: mode of inheritance? Repeat?

Answer 51

AR | GAA

Question 52

Spinal and bulbar muscular atrophy: mode of inheritance? Repeat?

Answer 52

Sex linked recessive | CAG

Question 53

What are symptoms of huntington's disease?

Answer 53

– Involuntary movements – Cachexia – Psychiatric symptoms – Dementia

Question 54

what chromosome is affected in huntington disease?

Answer 54

4

Question 55

How many repeats will result in huntingtons?

Answer 55

36+ | normal people have up to 26

Question 56

Where are most severe changes in huntington's seen?

Answer 56

neostriatum (caudate and putamen)

Question 57

T/F- Neostriatum is most severely affected by gliosis | and neuronal loss in huntington's disease while Other brain regions show loss of neurons without gliosis

Answer 57

true

Question 58

T/F- ALS affect only upper motor neurons

Answer 58

FAlse, both upper and lower

Question 59

Does spinal muscular atrophy affect upper or lower motor neurons?

Answer 59

lower

Question 60

ALS incidence peaks at ___ years of age

Answer 60

75

Question 61

ALS incidence peaks at ___ years of age

Answer 61

75

Question 62

Are most cases of ALS sporadic or inherited?

Answer 62

sporadic

Question 63

20% of familial cases of ALS show a defect in _____

Answer 63

SOD1 gene

Question 64

Describe the gross pathology of ALS

Answer 64

– Muscle atrophy and wasting – Atrophy of spinal cord affecting primarily anterior motor roots – Atrophy of cranial motor nerves, esp XIIth – Cortical atrophy limited to precentral gyrus (motor strip)

Question 65

Where will you find histological degenerative changes in ALS?

Answer 65

• Anterior horn cells in spinal cord • Motor nuclei in brainstem • Betz cells (upper motor) in motor cortex -Degeneration of cortical spinal tracts

Question 66

Anterior horn cells in ALS may show _____ bodies

Answer 66

Bunina

Question 67

20% of familial cases of ALS show a defect in _____

Answer 67

SOD1 gene

Question 68

T/F- glial inclusions are limited to sporadic forms of OPCA (olivopontocerebrellar atrophy) and are not found in hereditary forms

Answer 68

true