Neurodegenerative Pathology

Question 1

Genetics are not a common etiology of Alzheimer’s in those older than _____.

Answer 1

85

Question 2

How does cortical atrophy appear on histologic exam?

Answer 2

Astrocytic gliosis (status spongiosus)

Question 3

Neurofibrillary tangles appear on what kind of stain?

Answer 3

A silver stain (same one used by Alois Alzheimer’s)

Note: Silver stains do not pick up beta-amyloid plaques –only neurofibrillary tangles

Question 4

The modern version of the silver stain is _____________.

Answer 4

immunohistochemical staining for tau and amyloid (which can detect pretangles)

Question 5

Neurofibrillary tangles are composed of ___________.

Answer 5

hyperphosphorylated tau protein

Question 6

Neurofibrillary tangles reside where?

Answer 6

Within the cytoplasm

Question 7

Where do neurofibrillary tangles start (anatomically)?

Answer 7

In the transentorhinal cortex –the lower, lateral portion of the hippocampus

Question 8

The amorphous material in the center of plaques is ___________.

Answer 8

beta-amyloid

Question 9

What is a neurite?

Answer 9

A dead axon, “blown up” with tau protein

Question 10

What is amyloid angiopathy?

Answer 10

Deposition of amyloid within blood vessels that stain in Congo staining; not diagnostic of Alzheimer’s, but very commonly seen – also seen in those without Alzheimer’s

Question 11

The ABC system for describing the pathology of Alzheimer’s is ______________.

Answer 11

Amyloid deposition
Braak neurofibrillary stage
CERAD neuritic plaque density score

Final score breaks down to not, low, intermediate, high burden of disease.

Question 12

Frontotemporal dementia can present as one of two forms: _______________.

Answer 12

progressive aphasic (40%) or behavioral (60%)

Question 13

What protein does frontotemporal dementia present with?

Answer 13

TDP-43 = TAR-DNA binding Protein (this is ubiquitin positive tau, also found in ALS)

Question 14

What cellular deposit is sometimes found (sparsely) in the anterior horn neurons of those with ALS?

Answer 14

Bunina bodies and ubiquitin-reactive inclusions

Question 15

What protein accumulates in those with Parkinson’s?

Answer 15

Alpha-synuclein

Question 16

The second-most common cause of dementia is ___________.

Answer 16

Lewy body dementia (this is when they present with dementia and then develop Parkinson’s)

Question 17

Lewy body dementia causes profound atrophy in the __________ system.

Answer 17

limbic

Question 18

On H&E staining, how do beta-amyloid plaques appear?

Answer 18

As amorphous pink globules with microglia and astrocytes radiating outward

Question 19

Pick’s disease is a type of frontotemporal dementia that presents with ___________.

Answer 19

aphasia

Question 20

Again, what are the four key features of Parkinson’s disease?

Answer 20

Hypokinesia/bradykinesia
Resting tremor
Cogwheel rigidity
Postural instability

Question 21

What are some sources of non-idiopathic Parkinson’s?

Answer 21

Trauma (dementia pugilistica –Muhammad Ali)
Flu (particularly the Spanish flu of 1918)
MPTP (a contaminant of street drugs)
Familial Parkinsonism

Question 22

Other than the substantia nigra, what structures are damaged in the brains of those with Parkinson’s?

Answer 22

The locus ceruleus

Question 23

What presentation is typical of those with Lewy body dementia?

Answer 23

Progressive cognitive decline
Fluctuating states of consciousness and attention
Visual hallucinations (usually well-formed)
Spontaneous features of Parkinson’s

Question 24

Those with Huntington’s have more than the usual amount of ______ CAG repeats on chromosome ____.

Answer 24

11 - 34; 4

Question 25

__________ transmission of the Huntington’s gene leads to earlier onset.

Answer 25

Paternal