Block 4 Path Exam -- Neurodegenerative Diseases

Front 1

What are the two major classes of symptoms in ND diseases?

Back 1

Dementia
Movement disorders

Front 2

What two diseases account for the vast majority of dementia?

Back 2

Alzheimer's disease
Dementia w/ Lewy bodies

Front 3

2 dementias w/ temporoparietal & frontotempororparietal involvement

Back 3

Alzheimer's disease
Dementia w/ Lewy bodies

Front 4

Diseases that entail fronotemporal and lobar atrophy (4)

Back 4

Pick's disease
MND-inclusion dementia
Dementias of frontal type (DFT)
Chromosome 17-linked dementia

Front 5

5 main groups of Alzheimer's disease

Also, which one is the most common?

Back 5

Sporadic late onset AD
Familial late onset
Familial early onset
AD assoc. w/ Down's syndrome
AD assoc. w/ other ND disease


Sporadic late onset AD is the most common

Front 6

% of cases of AD that have a strong family history

Back 6

10%

Front 7

What is the AD1 gene due to?

Back 7

APP gene mutations on chromosome 21

Front 8

What is the AD2 gene assoc. w/?

Back 8

ApoE epsilon4 allele on chromosome 19

Front 9

What is the AD3 gene assoc. w/?

Back 9

Mutations in the presenilin-1 gene on chromosome 14

Front 10

What is the AD4 gene assoc. w/?

Back 10

Mutations in the presenilin-2 gene on chromosome 1

Front 11

Typically, how long do Alzheimer's pts. survive after onset of the disease?

Back 11

Typically, 5-7 years
(range is from 6 months - 15 years)

Front 12

Proteins implicated in cytoskeletal alterations in AD (NFTs & NPs)

Back 12

Abnormal hyperphosphorylated MAP Tau

Ultimately, beta-amyloid is deposited

Front 13

Type of stain that highlights NPs and NFTs in AD

Back 13

Bielschowsky silver

Front 14

How does AD atrophy in different brain lobes compare?

Back 14

Frontal = Temporal > Parietal > Occipital

Front 15

CERAD and B&B score combo for high probability of AD causing dementia

Back 15

CERAD frequent + B&B V/VI

Front 16

CERAD and B&B score combo for intermediate probability of AD causing dementia

Back 16

CERAD moderate + B&B III/IV

Front 17

CERAD and B&B score combo for low probability of AD causing dementia

Back 17

CERAD infrequent + B&B I/II

Front 18

Where in a neuron are Marinesco bodies found?

Back 18

In the nucleus

Front 19

Clinical manifestations of Dementia w/ Lewy bodies (4)

Back 19

Prog. cog. decline w/ persistent memory impairment
FLUCTUATING cognition w/ VARIATION in attention/alertness
Recurrent visual hallucinations
Spontaneous motor features of Parkinsonism

Front 20

Brain locations in which pallor is seen in dementia w/ Lewy bodies

Back 20

Substantia nigra & locus ceruleus

Front 21

Proteins that Lewy bodies contain that are useful to stain for

Back 21

Alpha-synuclein
Ubiquitin

Front 22

What neurochemical deficits are assoc. w/ Dementia w/ Lewy bodies?

Back 22

Dopaminergic deficit in cortical & subcortical areas

Severe cortical cholinergic deficit

Front 23

One of the main features that distinguishes frontotemporal dementias

Back 23

Deterioration in PERSONALITY and social function

Front 24

Histological features seen in Pick's Disease (2)

Back 24

Pick's bodies
Spongiform cortical degeneration (NOT due to CJD)

Front 25

What are the gyri described as in Pick's disease?

Back 25

"Blade-like" or "knife-edge"

Front 26

What stains do Pick's bodies stain positive for?

Back 26

Silver positive
Tau, Ubiquitin positive

Front 27

What areas of the brain are Pick's bodies primarily found in (2)?

Back 27

Hippocampus (pyramidal neurons & dentate gyrus)
Cortical layers II & III

Front 28

Mutation in what is the problem in chromosome-17 related dementia?

Back 28

The codon region of the Tau gene

NOTE: there are Tau-immunoreactive inclusions

Front 29

Where are inclusions most often found in FTD w/ ubiquitin inclusions?

Back 29

Dentate gyrus
Entorhinal cortex
Layer II of the cortex

Front 30

What does Tau protein do?

Back 30

Binds to microtubles, promoting assembly

Front 31

What differentiates different Tau protein isoforms?

Back 31

The microtubule-binding repeats

Front 32

Diseases in the Sporadic category of prion diseases (2)

Back 32

Creutzfeldt-Jakob disease
Fatal insomnia

Front 33

Diseases in the Dominantly Inherited category of prion diseases (3)

Back 33

Familial CJD
Gerstmann-Straussler-Scheinker Syndrome
Familial fatal insomnia

Front 34

Diseases in the Acquired category of prion diseases (3)

Back 34

Kuru
Iatrogenic CJD
New variant CJD

Front 35

Hallmark histological change in prion diseases

Back 35

Microvacuolation (spongiform change)

Front 36

What is PrP(c)?

Back 36

Prion protein
Normally expressed, membrane-assoc. protein (unknown function)

Front 37

When PrP accumulates, what does it form?

Back 37

Amyloid
PrP(c), which is normal, becomes PrP(p), abnormal

Front 38

How is PrP(p) different from PrP(c)?

Back 38

Conformationally different
Protease resistant

NOTE: PrP(p) induces further conversions of PrP(c) to PrP(p)

Front 39

Point mutation/insertion assoc. w/ susceptibility to GSS?

Back 39

PRO(102) --> LEU

Front 40

What is the importance of polymorphism at codon 129?

Back 40

Susceptibility factor for prion diseases

Over 90% of sCJD are homozygous for either M or V at 129

Front 41

Diseases within the category Synucleopathies

Back 41

PD
MSA

Front 42

Diseases within the category Tauopathies

Back 42

Progressive Supranuclear Palsy (PSP)
Corticobasal Degeneration (CBD)

Front 43

Clinical triad of PD

Back 43

Bradykinesia
Rigidity and postural abnormalities
Reting tremor

Front 44

When is the typical onset of PD?

Back 44

Later in life (5th decade)

Front 45

What does MPTP do?

Back 45

Depletes dopamine stores
Destroys dopaminergic neurons

Front 46

Areas where neurodegeneration selectively happens in PD

Back 46

Pars compacta of the substantia nigra
Retrorubral and ventrotegmental areas of midbrain

Front 47

% of neurons that have to be depleted before PD symptoms appear

Back 47

80-85% of nigral neurons
(80% of striatal dopamine content)

Front 48

Gross findings in MSA (4)

Back 48

Atrophy of cerebellum, middle cerebellar peduncles, and pons
Pallor of SN and LC
Atrophy & gray/brown discoloration of putamen
GLIAL CYTOPLASMIC INCLUSIONS

Front 49

Inclusions in MSA are positive for what?

Back 49

Silver, Tau, Ubiquitin, alpha-synuclein, TUBULIN

Front 50

Where are large numbers of inclusions present in MSA (2)?

Back 50

Pons and putamen

Front 51

Gross findings in PSP (2)

Back 51

Depigmentation of SN and LC
Atrophy of midbrain, pons, GP

Front 52

Microscopic findings in PSP

Back 52

GLOBOSE TANGLES (basophilic, rounded tangles)
[silver +, tau immunoreactive]

Abnormal Tau accumulation in neurons and glia
Neuronal loss & astrogliosis

Front 53

Other NDD that can present w/ PSP-like symptoms (3)

Back 53

Lewy body diseases
CBD
CJD

Front 54

Diseases w/ a course and pathology similar to PSP (3)

Back 54

CBD
Postencephalitic Parkinsonism
Alzheimer's disease

Front 55

Microscopic findings in CBD (4)

Back 55

Swollen cortical neurons (neuronal achromasia)
Neuronal loss and microvacuolation in the cortex
Gliosis
Abnormal Tau accumulation in neurons and glia (like in PSP)

Front 56

Diseases that entail large numbers of swollen neurons (3)

Back 56

CBD, Pick's disease, CJD

Front 57

Diseases that entail small numbers of swollen neurons (3)

Back 57

Lewy body dementia, Alzheimer's, MND-inclusion dementia

Front 58

Diseases that entail basal/cortical Tau-related pathology (2)

Back 58

PSP & CBD
(remember, there are abnormal Tau accumulations in neurons and glia)

Front 59

Trinucleotide repeat seen in Friedreich's ataxia

Back 59

GAA

Front 60

Type of inheritance seen in Huntington's disease

Back 60

Autosomal Dominant

Front 61

Number of CAG repeats seen in Huntington's disease

Back 61

37 - 100 (or more)

NOTE: # of repeats inversely correlates to age of disease onset

Front 62

What is genetic anticipation?

Which neurodegenerative disease covered displays it?

Back 62

Later generations being affected earlier and more severely

Huntington's disease demonstrates anticipation

Front 63

What type of transmission is most common in Juvenile onset HD?

Back 63

PATERNAL

Front 64

What type of transmission is most common in Late Onset HD?

Back 64

MATERNAL

Front 65

What form of HD is the most common?

What are some of the features of it?

Back 65

Hyperkinetic
(Mid-life and late-onset)

Choreiform movements, EARLY psych disease
Slow progression (17 yr duration)

Front 66

What types of HD are assoc. w/ the akinetic-rigid form?

Back 66

Juvenile and early onset

NOTE: this disease progresses rapidly

Front 67

Types of HD and their corresponding age ranges

Back 67

Juvenile onset (4-19 yo)
Early onset (20-34 yo)
Mid-life onset (35-49 yo)
Late onset (> 49 yo)

Front 68

What areas are usually sig. atrophied in HD?

Back 68

Caudate, putamen, and pallidus
(variable cerebral atrophy is seen)

Front 69

Abnormal neuritis in HD is positive for what?

Back 69

Ubiquitin

Front 70

3 Inherited MNDs and their types of inheritance
(motor neuron diseases)

Back 70

Spinal Muscular atrophy (aut. recessive)
Kennedy's syndrome (X-linked)
Familial ALS (aut. dominant)

Front 71

What types of neurons are affected in ALS?

Back 71

MOTOR neurons
(BOTH upper and lower)

Results in muscle atrophy and hyper-reflexia

Front 72

When does ALS usually have its onset?

What group of people is more prone to get it?

Back 72

5th-6th decade

Male predominance (2:1)

Front 73

In familial ALS, what is mutated?

Back 73

Gene coding for Cu/Zn superoxide dismutase 1

Front 74

What 3 major groups of neurons are involved in ALS?

Back 74

Anterior horn neurons of SC
Motor nuclei of brain stem (particularly the HYPOGLOSSAL)
UMNs of the cerebral cortex

Front 75

How is intellectual capacity affected by ALS?

Back 75

It is not