Neurodegenerative Diseases - Random Order!!!

Question 1

Corticobasal Degeneration - presentation and Pathology

Answer 1

Parkinsonism + Alien Limb Phenomenon + Asymetric motor signs + Dementia

see ballooned, achromatic neurons

**tau+ inclusions **

deep gray matter and brainstem

Question 2

Variant Creutzfeldt-Jakob disease differences from regular CJD?

Answer 2

Younger Age at onset

Longer disease duration

+Florid Plaques: amyloid core surroudnded by spongiosis

PrPsc detectable in lymphoid tissue

MAd Cow Disease

Question 2

Chronic Traumatic Encephalopathy - what happens and what are symptoms and pathology?

Answer 2

Consequence of repetitive mild TBI (concussions) and get symptoms 8-10 yrs later

Symptoms include **irritability, impulsivity, aggression, depression, short term memory loss, and heightened suicidality **

See Tau Accumulation in patchy distribution - focal areas of increased tau at the cortical surface and in depths of sulci

Increased reactivity in Amygdala

Question 3

What do you see in Binswanger’s disease - subtype of vascular dementia?

Answer 3

White Matter Degeneration secondary to vascular disease - can look like a Leukodystrophy!!!

See **Small Artery Sclerosis **

Severe Arteriosclerosis + WM Damage = Binswangers

Question 4

Lewy Body Dementia - Presentation!!!!!! And patholgy

Answer 4

Presentation: *Fluctuating Cognition - 2nd most common form of dementia

**Personality changes, visual hallucinations, and LATER get Parkinsonism **

Cortical Disease process occurs first and get Lewy Bodies and Lewy Neurites that are synuclein positive in cortex, brainstem and limbic system

Question 4

What the heck is CADASIL eh?

Pathology?

Gene involvement?

Answer 4

*Cerebral Autisomal Dominant Angiopathy with Subcortical Infarcts and Leukoencephalopathy *

**NOTCH 3 Mutation!!!! **

See White Matter Degeneration and infarcts

Vascular thickening with PAS+ Deposits

Also present in BV in skin

Question 5

Synucleinopathies - what’s happening there?

What are some examples of them?

Answer 5

See Neurodegeneration + accumulation of Alpha-synuclein

Parkinson’s Disease

Lewy Body Dementia

Multiple System Atrophy (Alpha-synucliein + Oligodendrocytes)

Question 5

Pathology in FTD with Parkinsonism?

Pathology in FTD with Motor Neuron disease?

Answer 5

FTD+P = Tau positive Neurofibrillary tangles, Frontotemporal degeneration and degeneration of Substantia Nigra

FTD+ALS = Frontotemporal degeneration and **TDP-43+ Inclusions **

Question 6

Progressive Supranuclear Palsy - Presentation and Pathology

Answer 6

PSP = Parkinsonism + Taupathy!!!!!!!

Parkinsonism + **Vertical Gaze Paralysis **

see Tau+ Neurofibrillary degeneration in neurons AND glia in deep gray matter and brainstem

Question 7

What are the 3 forms of Vascular Dementia?

Answer 7

Multiple Infarct Dementia

Binswanger’s Disease

CADASIL

Question 8

Creutzfeltdt Jakob Disease - Pathology and Presentation

Answer 8

Presentation: Rapidly progressive dementia, Startle Myoclonus, **Period Sharp Waves on EEG **

-middle age or older

see PrPsc instead of normal Pr (chromosome 19) and get Spongiform degeneration of Gray Matter

Question 10

Genes involves in Alzheimer’s Disease?

Answer 10

_Familial Early Onset AD: _

Chromosome 21 - (seen with Down Syndrome) Gene for Beta Amyloid Precursor Protein

Chromsome 14 - Presenilin 1

Chromosome 1 - Presenilin 2

*Beta-APP is cleaved by beta and gamma secretase encoded for by the Presenilin genes *

Late onset AD: Apolipoprotein E4 allele

E4 involved in lipid transport

Question 11

Multiple System Atrophy - Presentation and Pathology

Answer 11

Parkinsonism (with poor response LDOPA) + Ataxia + Autonomic Failure

***Alpha-synuclein positive OLIGODENDROGLIAL cytoplasmic inclusions

Striatonigral degeneration

Olivopontocerebellar degeneration (cerebellum and inf olivary nuerons)

Shy-Drager syndrome - pregangionic sympathetic neuron loss - degeneration of **intermediolateral cell column of SC **

Question 13

Parkinson Disease = Pathology and genetics

Answer 13

Loss of **Da Neurons in Substantia Nigra **

See Lewy Bodies (Synuclein positive eosinophilic inclusion with halo around it ) in Substantia nigra

Familial Disease linked to Alpha-synuclein PARK1 Genes

Question 15

What is Parkinsonism?

Answer 15

Presentation of Rigidity, Bradykinesia, and Tremor

Question 16

ALS Presentation and Pathology

Gene?

Answer 16

**Muscle WEakness/wasting but cognition preserved (except for 10% also have FTD) **

Degeneration of Upper and Lower Motor Neurons

Lower = Neurogenic atrophy of skeletal muscles (Amyotrophy)

Upper = Lateral Column Degeneration ( Wallerian Degeneration)

See Bunina Bodies and TDP43+ inclusions in motor neurons

small percentage of Cu-Zn Superoxide Dismutase Germline Mutations (SOD1)

Question 17

Clinical PResentation of Alzheimer’s Disease?

Pathology of Alzheimer’s Disease?

Answer 17

Progressive Memory Loss + Dysfunction in at LEAST one other cognitive domain

See Amyloid plaques (Amyloid beta staining with congo red to see beta-pleated sheets)

see Neurofibrillary tangles with Tau

Question 18

What are the 3 types of Fronto-temporal Dementia?

General Pathology of FTD?

Answer 18

Pick Disease

FTD with Parkinsonism linked to Chromosome 17 (tau)

FTD with motor neuron disease - spectrum of ALS

In general, see atrophy of FT lobes - knife blade atrophy

dementia with lots of accumulations that are non-AD and non-LB

Question 19

Most common cause of familial FTD and ALS worldwide?

Answer 19

Most sporadic but some from C9orf72 hexanucleotide repeat expansion

Question 20

Tauapathies - in general what’s happening?

What are examples of Taupathies?

Answer 20

See neurodegenerative diseases with** accumulation of phosphorylated tau**

Tau is a microtubule associated protein on **Chromosome 17 **

Picks Disease and FTD

Progressve Supranuclear palsy

Corticobasal Degeneration

Chronic Traumatic Encephalopathy

Alzheimer’s Disease

Question 21

Pick Disease PResentation and Pathology

Answer 21

Presentation - Language Dysfunction, Personality changes, Memory Loss

Tau-positive Pick Bodies (rounde dinclusins +tau stain) and **Ballooned neurons **