DEGENERATIVE DISEASES AFFECTING THE CEREBRAL CORTEX-Alzheimer Disease Flashcards
The major cortical degenerative disease is________
Alzheimer disease,
What is the principal clinical
manifestation of alzeimer’s disease?
dementia, that is, progressive loss of cognitive function independent of the state of attention.
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).
- *Regardless of etiology**, dementia is
- *not part of normal aging** and always represents a pathologic process.
____________) is the most common cause of dementia in the elderly.
Alzheimer disease (AD)
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, indicatingsevere cortical dysfunction.
Eventually, in 5 to 10 years, the
affected individual becomes profoundly disabled, mute, and immobile.
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. **
This progressive
increase in the incidence of the AD with age has given rise to major medical, social, and
economic problemsin 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
What is the definitive diagnosis of AD?
While pathologic
examination of brain tissueremainsnecessary 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.
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 parenchymaand reduced brain volume.
Structures of the medial temporal lobe, including hippocampus, entorhinal cortex and
amygdala,areinvolved early in the courseand are usuallyseverely atrophied in the later
stages.
What is the major microscopic abnormalitiy in AD which also forms the basic histologic diagnosis?
** neuritic (senile) plaque**s 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.
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,whichmay 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.
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).
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 ).
Aβ
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
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. **
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.
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.
What are Neurofibrillary tangles?
These are bundles of filaments in the cytoplasm of the neurons that
displace or encircle the nucleus.
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.
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.
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”