lecture 10 - - Neurodegnerative disease, Vascular Dementia, and Prion Disease

Question 1

Prion Disease -- 
how common? 
Three forms? 
Which is the most common form? 
Biochemistry of the disease

Answer 1

1-2 cases per Million per years

Three forms: Familial, Sporadic, transmitted

Most common: Sporadic

Biochem: PRPC protein –> PRPSC which forms abnormal beta sheets resistant to proteases

Question 2

Two human forms of prion disease and associated pathology?

Answer 2

Cruetzfeldt Jakob Disease –

Variant Form CJD

Question 3

CJD
pathology?
Median Survival?
Manifestations?

Variant CJD – how is it acquired ?

Answer 3

CJD:

Spongiform Degeneration of the gray matter with vaculoization –

Rapidly progressive (median survival 3.5 months) of dementia and startle myoclonus

Variant CJD – thought be acquired through contaminated beef

Question 4

What are the synucleinopathies ?

Answer 4

PD
LBD
Multiple System Atrophy

Question 5

What are the Tauopathies ?

what other disease?

Answer 5

Fronto-Temporal Dementia (Pick’s Disease, FTDP-17)

PSP – Progressive Supranuclear Palsy

Corticobasal Degeneration

(ALZ – tangles = tau; senile plaques = beta)

Question 6

what is vascular dementia?

what are the three subtypes

Answer 6

Vascular dementia – Brain injury from vascular insufficeincy/ischemia/HTN

Step wise progression rather than gradual decline

Subtypes:
Multiple Infarct Dementia
Biswanger’s Disease
CADASIL –

Question 7

CADASIL

stands for?
associated mutation?
Pathological changes?
how is a dx typically conducted?

Answer 7

Cerebral Autosomal Dominant Angiopathy w/ Subcortical Infarcts and Leukoencephalopathy

(CVD and white matter damage)

Molecular – Notch 3 Mutation

Sclerotic Changes, which can also be present on the skin (therefore skin bx is taken for Dx)

Question 8

Binswangers

Answer 8

white matter degeneration secondary to vascular disease (small artery sclerosis)

Question 9

alz --
histopath findings
Imaging
pathogenesis 
potential treatments

Answer 9

Tau Tangles; Beta Amyloid Senile Plaques
Imaging: Ventricular englargement with Sulcal Widening

Pathogensis: ApoE4 increased risk for development;
Mutated genes for Presnelin 1 and 2 – involved in metabolism of Beta Amyloid
Plaques = A-Beta Fragement of the Beta Amyloid

Tx - Increased ACH
Cholinesterase Inhibitors –
NMDA Antagonist – Memantine (neuroprotective)

Question 10

PD –
Gross path
Micropath

What are parkinsonisms?

Possible treatment

Answer 10

Gross Path – loss of pigment of the SN

Micropath – Lewy Bodies in the SN
Loss of dopaminergic neurons

Parkinsonism – Bradykinesia, Unilateral tremor, ridigity

Treatments: LevoDopa with dopamine metabolizing enzyme inhibitor (Carbidopa)

Other treatments – MAOIs (block dopamine reuptake); COMT inhibitors; Dopamine Agonists

Question 11

Lewy Body Dementia –

how does it differ from PD

Answer 11

Clinical onset for LBD: dementia first, then parkinsonisms

PD: Parkinsonism first

Question 12

Multiple System Atrophy –
what 3 regions are damaged and how does the damage manifest

where does the synulcein accumulate?

Answer 12

SN – dopamine loss = Parkisonisms

Olivopontocerebellar damage = ataxia

Preganglionic Neuron Autonomic Loss = Shy drager autonomic loss

Synuclein accumulates in oligodendrocytes (not neurons like PD)

Question 13

Tauopathies:

Answer 13

Fronto temporal dementia (Picks and FTD-Parkinsonism Chr 17)

Progressive Supranuclear Palsy

Corticobasilar Degeneration

Question 14

What are the Frontotemporal Dementias –

how do they manifest ?

Answer 14

Pick’s and FTDP_Chr17

Language dysfunction, personality changes, memory loss , dementia

Question 15

Pick’s Disease –

Characterisitic pathology?

Answer 15

Tau positive Pick bodies; ballooned neurons

Question 16

Progressive Supranuclear Palsy –

Characteristic symptoms?

Answer 16

Vertical gaze ophthalamoplegia + Parkinsonism

Question 17

Corticobaslilar Denengeration

Characteristic Symptoms?

Answer 17

Alien Limb Phenomena + Parkinsonisms + Alien Limb

Question 18

ALS -- 
damage to what?
Etiology? 
muBUntation? 
Characteristic Pathology?

Answer 18

UMN and LMN damage

Etiology – idiopathic
Minority associated with mutation to SOD1

Characterisitc path – Bunina bodies and TDP43 Inclusions

Question 19

Is Chronic Truamatic Encephalopathy a tauopathy or synucleinopathy?

Answer 19

Tauopathy