Path: Degenerative Diseases Flashcards
What gross features are affected in ALS?
Motor Neurons in the cerebral cortex and spinal cord.
Motor nuclei in the brainstem
Characteristic feature of neurons in the substantia nigra on histological slides in patients with PD.
Lewey Bodies
Common presentation of muscle cells in a biopsy from a patient with ALS.
Grouped Atrophy
Where do the symptoms of ALS begin in most patients?
Hands and feet, usually begins with weakness and muscle atrophy.
Does ALS manifest as an UMN or LMN lesion?
Both
What genetic characteristic does Huntington Disease display?
Anticipation
What is at increased risk in patients with Huntington Disease?
Suicide
-patients have a parent die from the disease and will get genetic testing indicating the defective HD gene. Once they start to notice symptoms they commit suicide rather than slowly progress through the disease
What is the most common inherited ataxia?
Friedreich ataxia
What is the mechanism of Friedreich Ataxia?
Genetic Defect (frataxin protein-he wasn’t too concerned with this) that leads to degeneration of the cerebellum and spinal cord. The posterior and lateral columns shrink leading to ataxia in all four limbs starting with lower limbs.
Stretch reflexes become lost, vibratory and position sense disappear. (+) Babinski sign.
Leading cause of senility (dementia).
Alzheimer Disease
What are the two cellular associations indicative and required to confirm a diagnosis of Alzheimer Disease?
- Amyloid Beta Plaque
2. Neurofibrillary Tangles
How do Amyoid Beta Plaques form and how do they lead to Alzheimer Disease?
Amyloid Beta protein is processed from Amyloid Precursor Protein (APP) and normally functions as a transcription factor to regulate cholesterol. (not important)
Sometimes these proteins can be secreted into the extracellular matrix and become “sticky” leading to agglutination and formation of plaques. These plaques will adhere to the outside of a neuron and the host immune system will try to eliminate the plaques, destroying the neurons in the process.
How do the neurofibrillary tangles form and how do they lead to Alzheimer Disease?
Normally a protein called tubulin holds the microtubules within a cell together to act as a transport highway within the cell. The gene that makes this protein becomes mutated and is termed the “tau” protein. Tau proteins cannot allow proper formation of microtubules. These tau proteins become phosphorylated and lead to the “tangles”.
Without this “highway” the neurons cannot divide or carry out necessary processes and eventually die.
How does Mercury toxicity lead to Alzheimer-like disease?
Similar to the formation of Neurofibrillary tangles.
Mercury binds tubulin preventing the binding of GTP. Without the binding of GTP, multiple tubulin proteins cannot bind together to make the microtubules and the neurons die.
How can amyloid plaques be observed on biopsy?
Congo red is a stain used that will bind to the amyloid plaque proteins. This is not the only thing Congo red binds and is therefore NOT diagnostic.
The stain is then observed under polarized light and any amyloid plaques will appear “apple green”. This IS diagnostic.
