DEGENERATIVE DISEASES AFFECTING THE CEREBRAL CORTEX-Alzheimer Disease Flashcards Preview

2H. Pathology- CNS > DEGENERATIVE DISEASES AFFECTING THE CEREBRAL CORTEX-Alzheimer Disease > Flashcards

Flashcards in DEGENERATIVE DISEASES AFFECTING THE CEREBRAL CORTEX-Alzheimer Disease Deck (56)
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1

The major cortical degenerative disease is________

 Alzheimer disease,

2

What is the principal clinical
manifestation of alzeimer's disease?

dementia, that is, progressive loss of cognitive function independent of the state of attention. 

3

There are many other causes of dementia, including the various forms of
___________ 

These diseases also involve subcortical structures, but many of the clinical symptoms are related to the changes in the cerebral cortex.

 

  • frontotemporal dementia,
  • vascular disease,
  • dementia with Lewy bodies (considered later in the context of Parkinson disease,
  • the other Lewy body disorder),
  • CJD, and neurosyphilis (both considered earlier).

4

Regardless of etiology, dementia is
not part of normal aging and always represents a pathologic process.

5

____________) is the most common cause of dementia in the elderly. 

Alzheimer disease (AD)

6

When does AD becomes clinically apparent?

The disease
usually becomes clinically apparent as insidious impairment of higher intellectual function, with
alterations in mood and behavior.

Later, progressive disorientation, memory loss, and aphasia
become manifest
, indicating severe cortical dysfunction.

Eventually, in 5 to 10 years, the
affected individual becomes profoundly disabled, mute, and immobile.

 

7

AD Patients rarely become
symptomatic before 50 years of age, but the incidence of the disease rises with age, and the
prevalence roughly doubles every 5 years, starting from a level of_____________

 1% for the 60- to 64-year-old
population

and reaching 40% or more for the 85- to 89-year-old cohort. 

8

This progressive
increase in the incidence of the AD with age has given rise to major medical, social, and
economic problems
in countries with a growing number of elderly individuals.

Most cases are
__________, and although 5% to 10% are familial, the study of such familial cases has provided
important insight into the pathogenesis of the more common sporadic form.

 

sporadic

9

What is the definitive diagnosis of AD?

While pathologic
examination of brain tissue
remains necessary for the definitive diagnosis of Alzheimer disease,
the combination of clinical assessment and modern radiologic methods allows accurate diagnosis in 80% to 90% of cases.

10

What is the gross appearance of AD?

 

 

Grossly, the brain shows a variable degree of cortical atrophy marked by
widening of the cerebral sulci that is most pronounced in the frontal, temporal, and parietal
lobes
( Fig. 28-36 ).

With significant atrophy, there is compensatory ventricular enlargement
(hydrocephalus ex vacuo)
secondary to loss of parenchyma and reduced brain volume.


Structures of the medial temporal lobe, including hippocampus, entorhinal cortex and
amygdala,
are involved early in the course and are usually severely atrophied in the later
stages.

11

What is the major microscopic abnormalitiy in AD which also forms the basic histologic diagnosis?

 neuritic (senile) plaques and neurofibrillary tangles.

There is progressive
and eventually severe neuronal loss and reactive gliosis in the same regions that bear the
burden of plaques and tangles.

12

 What are neuritic plaques in AD?

Neuritic plaques are focal, spherical collections of dilated, tortuous, neuritic processes
(dystrophic neurites)
often around a central amyloid core, which may be surrounded by clear
halo
( Fig. 28-37A ).

Neuritic plaques range in size from 20 to 200 μm in diameter; microglial cells and reactive astrocytes are present at their periphery.

 

13

 

In AD where can you find the Plaques ?

 

  • hippocampus,
  • amygdala,
  • and neocortex,
  • although there is usually relative sparing of primary motor and sensory cortices (this also applies to neurofibrillary tangles). 

14

In AD the amyloid core, which can be stained by Congo Red, contains several abnormal proteins. The dominant component of the amyloid plaque core is ________, a peptide derived through specific processing
events from a larger molecule, amyloid precursor protein (APP) ( Figs. 28-37 and 28-38 ).

15

The two dominant species of Aβ, called _____and  ____________, share an Nterminus and differ in
length by two amino acids at the C-terminus.

Other proteins are present in plaques in lesser
abundance, including components of the complement cascade, pro-inflammatory cytokines,
α1-antichymotrypsin, and apolipoproteins.

 

Aβ40 and Aβ42

16

What are diffuse plaques in AD?

In some cases, there is deposition of Aβ peptides
with staining characteristics of amyloid in the absence of the surrounding neuritic reaction.
These lesions, termed diffuse plaques, are found in superficial portions of cerebral cortex as well as in basal ganglia and cerebellar cortex. 

 

17

What appears to represent an early stage of plaque dev in AD?

Diffuse plaques appear to represent an
early stage of plaque development.

This conclusion is based primarily on studies of brains
from individuals with trisomy 21.

Recall that in patients with trisomy 21 (Down syndrome), early
onset of Alzheimer disease is common
( Chapter 5 )

. In some brain regions (cerebellar cortex
and striatum) these diffuse plaques represent a major manifestation of the disease, with other
clear-cut findings of Alzheimer disease, or in isolation.

 

18

In some brain regions (cerebellar cortex
and striatum) these diffuse plaques represent a major manifestation of the disease, with other
clear-cut findings of Alzheimer disease
, or in isolation.

While neuritic plaques contain both A
β40 and Aβ42,
diffuse plaques are predominantly made up of ________

Aβ42.

19

What are Neurofibrillary tangles?

These  are bundles of filaments in the cytoplasm of the neurons that
displace or encircle the nucleus.

 

20

How are AD neurofibillary tangles in pyramidal neurons?

In pyramidal neurons, they often have an elongated “flame”
shape; in rounder cells, the basket weave of fibers around the nucleus takes on a rounded
contour (“globose” tangles). Neurofibrillary tangles are visible as basophilic fibrillary  structures with H&E staining ( Fig. 28-37C ) but are dramatically demonstrated by silver
(Bielschowsky) staining ( Fig. 28-37D ).

 

C, Neurofibrillary tangle is present within one neuron, and several
extracellular tangles are also present (arrows). D, Silver stain showing a neurofibrillary
tangle within the neuronal cytoplasm.

21

Where can you commonly find neurofibrillary tangles?

They are commonly found in cortical neurons,
especially in the entorhinal cortex, as well as in other sites such as pyramidal cells of the
hippocampus, the amygdala, the basal forebrain, and the raphe nuclei.

22

Neurofibrillary tangles
are insoluble and apparently resistant to clearance in vivo, thus remaining visible in tissue
sections as______________tangles long after the death of the parent neuron.

 “ghost” or “tombstone” 

23

Ultrastructurally, neurofibrillary tangles are composed predominantly of ____________

paired helical filaments along with some straight filaments that appear to have a comparable composition.

 

24

What is the major compone​nt of paired helical filaments? 

major component of paired helical filaments is abnormally hyperphosphorylated forms of the protein tau,

25

What is a protein tau?

an axonal microtubule-associated protein that enhances microtubule assembly (Fig. 28-37E )

26

The other components of neurofibrillary tangles are:

Other components include MAP2 (another microtubule-associated protein) and
ubiquitin.

Paired helical filaments are also found in the dystrophic neurites that form the outer
portions of neuritic plaques and in axons coursing through the affected gray matter as
neuropil threads.

Tangles are not specific to AD, being found in other diseases as well.

27

In addition to the diagnostic features of plaques and tangles, several other pathologic findings: are seen in the setting of AD.

_________________ is an almost invariable
accompaniment of Alzheimer disease
; however, it can also be found in brains of individuals
without AD
(see Fig. 28-18B )

 Cerebral amyloid angiopathy (CAA).

 

 

28

What is Granulovacuolar degeneration?

It  is the formation of small (∼5
μm in diameter),
clear intraneuronal cytoplasmic vacuoles, each of which contains an
argyrophilic granule.

While it occurs with normal aging, it is most commonly found in great
abundance in hippocampus and olfactory bulb in AD.

 

29

What are Hirano bodies?

  • They are found especially in AD,
  •  elongated, glassy, eosinophilic bodies
  • consisting of paracrystalline arrays of beaded filaments,
  • with actin as their major component.
  • They are found most commonly within hippocampal pyramidal cells.

30

Since both plaques and tangles may be present in low abundance in nondemented
individuals, the diagnosis of Alzheimer disease is based on a ______________

combination of clinical and
pathologic features. 

 

Note: The progression of changes is fairly constant.