Overview

Question 1

AD is characterized by Extracellular accumulation of ____1____ and Intracellular accumulation of ____2____.

Answer 1

1. beta-A4 amyloid (plaques)
2. tau (neurofibrillary tangles and neuropil threads)

AD is characterized by extracellular accumulation of beta-A4 amyloid (plaques) and intracellular accumulation of tau (neurofibrillary tangles and neuropil threads)

Question 2

NFTs are composed of fibrillar aggregates (above) made of _____________.

Answer 2

paired helical filaments.

Question 3

CERAD (Consortium to Establish a Registry for Alzheimer’s Disease) criteria for the neuropathological diagnosis of AD is based on a clinical history of dementia and age-related numbers of ______________.

Answer 3

neuritic plaques

Question 4

NFTs are made of abnormal accumulations of _________________.

Answer 4

hyerphosphorylated tau protein

Question 5

In the late stages of AD, NFTs are frequent in neocortical areas and accompanied by numerous ______________.

Answer 5

neuropil threads

Question 6

NFTs changes are evaluated according to the _______________.

Answer 6

Braak staging system

Question 7

Parkinson’s Disease is characterized by loss of pigment in the _______ and ________.

Answer 7

substantia Nigra & locus ceruleus

Question 8

Neuronal loss in the substantia nigra is accompanied by _______ and _______.

Answer 8

numerous pigment-laden macrophages (melanophages, arrow) and gliosis

Question 9

Lewy bodies are abnormal aggregates of _____1_____.
Immunostaining for _____1_____ strongly labels both Lewy Bodies and Lewy neurites in the substantia nigra. Both are also immunoreactive to ____2____.

Answer 9

1. alpha-synuclein
2. ubiquitin

Question 10

Neurodegenerative diseases characterized by abnormal intracellular aggregation of alpha-synuclein (4):

Answer 10

Parkinson’s Disease
Dementia with Lewy Bodies
Lewy Body Variant of AD
Multiple System Atrophies
OPCA
SND
Shy-Drager Syndrome

Question 11

Which 5 brain areas are used for Lewy Body scoring?

Answer 11

Frontal, Cingulate, Temporal,, Transentorhinal, Parietal

Question 12

Gross findings in Pick’s Disease.

Answer 12

severe atrophy of the frontal and temporal lobes (lobar atrophy)
- with “knife-edge” atrophy of the gyri.

Question 13

Histologic findings in Pick’s Disease.
-Which other degenerative diseases show similar findings?

Answer 13

Cortical neuronal loss with intense gliosis
-FTLD

Question 14

Which immunostain will highlight Pick bodies?

Answer 14

Tau

Question 15

Progressive Supranuclear Palsy (PSP) typically shows severe depigmentation of the __________ and ___________.

Answer 15

substantia nigra and locus ceruleus

Question 16

The most common areas affected in PSP:

Answer 16

SUBSTANTIA NIGRA
GLOBUS PALLIDUS
SUBTHALAMIC NUCLEI
CN III
CN IV

hippocampus, entorhinal cortex, dentate nuclei, red nuclei, periaqueductal gray matter, colliculi, as well as CN X and XII nuclei.

Putamen, pontine nuclei, olivary nuclei, and cortex may also show GLOBOSE TANGLES

Question 17

_______________ characterize PSP and can be seen with silver stains (Gallyas).

Answer 17

Globose NFTs

Question 18

Progressive Supranuclear palsy (PSP)

T/F: Globose NFTs are tau-positive

Answer 18

True.

NOTE: Many glial cells also contain abnormal accumulations of tau.

Question 19

Huntington’s Disease - Gross findings.

Answer 19

Atrophy of basal ganglia (Severe)
Cortical atrophy (Mild)

Question 20

Huntington’s Disease
-Which groups of neurons are mostly affected?

Answer 20

aspiny (small, ACh+) neurons > Spiny (large, GABA+) neurons.

Question 21

Aspiny neurons:
-Size
-Neurotransmitter

Answer 21

-Small
-Acetylcholine (ACh)+

Question 22

Spiny neurons
-Size
-Neurotransmitter

Answer 22

-Large
-GABA+

Question 23

Huntington’s Disease.

Caudate atrophy is assessed using the ___________ ________ system

Answer 23

Vonsattel grading

Question 24

Amyotrophic Lateral Sclerosis (ALS):

ALS is characterized by loss of what cells?

Answer 24

Upper and Lower Motor Neurons

Question 25

Amyotrophic Lateral Sclerosis (ALS):

Gross findings

Answer 25

The spinal cord often shows atrophy of the cervical and lumbar enlargements as well as of the anterior spinal roots.

In some cases, atrophy of the pre-central gyrus can be observed.

Question 26

Amyotrophic Lateral Sclerosis (ALS):

In cervical and lumbar regions, the _____1_____ have numerous large _____2______ neurons which are lost in ALS.

Answer 26

1. anterior horns
2. Lower motor neurons

Question 27

Answer 27

In remaining LMN, there may be Bunina bodies (left) and large hyaline inclusions (right)

Question 28

Answer 28

Ubiquitin immunostains reveal some LMN with ubiquitin skeins.

Question 29

ALS - Myelin stain
-pathophysiology and areas affected

Answer 29

Loss of UMN leads to degeneration of motor axons
- resulting in pallor of the cerebral peduncles, pyramids (right, upper) and
both lateral and anterior corticospinal tracts in the spinal cord (right, lower)

Question 30

Answer 30

Loss of neurons in the motor cortex is accompanied by gliosis, which is lacking in the adjacent sensory cortex

Question 31

Prion Encephalopathies.

Prion protein is a normal abundant protein in the brain. The function is unknown. It has a normal secondary structure dominated by ______1______ formations and is easily digested by proteases

Abnormal prion protein (the cause of the prion diseases) is the same protein, but has a secondary structure dominated by ______2______, which makes it more prone to aggregate and resitant to protease digestion.

Answer 31

1. alpha-helical
2. beta-pleated sheets

Question 32

T/F. Most cases of CJD show little or no cerebral atrophy

Answer 32

True

Question 33

Characteristic histologic changes in CJD.

Answer 33

Spongiform changes of both cortical and deep gray matter, neuronal loss and gliosis characterize the CJD brain.

Question 34

In 15% of CJD cases “___1___” (prion) plaques can be found in the ____2____.

Answer 34

1. kuru
2. Cerebellum

Question 35

Gerstmann-Straussler-Scheinker (GSS).

GSS has numerous prion plaques primarily in the _________. There is little ________ change.

Answer 35

Cerebellum
Spongiform

Question 36

vCJD has distinctive pathology consisting of numerous cortical and cerebellar “______” plaques and moderate _______ change.

Answer 36

Florid
Spongiform

Question 37

HIV Encephalitis is characterized by ________________ and perivascular accumulations of ______________, most of which are HIV+

Answer 37

multinucleated giant cells
macrophages