Alz Disease and Frontotemporal Flashcards
How does the basal ganglia malfunction in Parkinson’s disease?
There is loss of the substania nigra – dopamine is not released to the Striatum.
–Preventing it from inhibiting the subthalamic nucleus and from inhibiting the globus pallidus interna
What does dopamine do with the D1 Receptor do in the Striatum?
Direct Pathway
– D1 Receptor – Activates striatum to release GABA inhibiting the Globus Pallidus interna – Stopping the “inhibition hold” on Thalamus
What is the action of dopamine binding to the D2/D4 receptors in the striatum?
Indirect Pathway
D2/D4 - Inhibit GABA release from the straitum to the Globus Pallidus Externa, which allows it to activate and release GABA to Subthalamic Nucleus. This prevents the Subthalamic nucleus from releasing Glutamate to Globus Pallidus Interna (usually “holds inhibition” of Thalamus)
What is the main pathology regarding Huntington’s Disease in the Striatum?
Loss of Cholinergic neurons, which are responsible for inducing release of GABA to Globus Palladus Externa.
–Subthalamic Nucleus permanently inhibiting – Not inhibition of the Thalamus = Unregulated Movement
How do neurologic cells accumulate damage over time?
Environmental Toxins - Damage Mito
Oxidative Stress - build up of ROS
Excitotoxicity - too much glutamate
– Basically not enough ATP is produced to fend off the damaging substances, or too much Ca+2 and its used up clearing it out, opening up the cell to damage
What are the clinical features of Alzheimer’s Disease?
- Progressive decline of recent memory
- Impairment of visuo-spatial functions
- Abstract thinking deabled
What are the key features of initial stages of Alzheimers?
- new learning is imparted
- mildly impaired remote recall
- disorientation periodic
- Poor Word List Generation – Animals
What are signs of progression of Alzheimer’s disease?
- More frequent disorientation
- Acalcula – Bad at Math
- Delusions-Pyschosis episodes
End stage of Alzheimers?
- Loss of basic life functions
- No sphincter tone or control
- loss of speech and mobility
If upon histology of patient you identify neurofibrillary tangles and neuritic extracellular plaques, what might the patient be suffering from?
Alzheimers Disease – histologic diagnosis
How do AB plaques develop?
Break down of Amyloid Precursor Protein by alternative pathway of B-secretase and Gamma-secretase – causing the products to aggregate and not degrade properly
– Usually flows through the Alpha-secretase pathway creating soluble products - No AB proteins.
What are the genetic risk factors for developing Alheizmers disease?
- Presenilin 1 – early onset
- ApoE – E4 variant – increased risk late
- Tau gene mutation – increased tau aggregation
- APP gene overactivation – Trisomy 21
Where do the plaques/tangles generally accumulate and how can they cause small hemorrhages?
- Frontal and Temporal Lobes
- - if they form at a vessel – cerebral amyloid angiopathy, can cause small hemorrhages
What happens to the brain grossly during Alzheimers?
- Atrophy of the Gyri
- Widened Sulci
- Increased Lateral Ventricles
- *Nonspecific for Alz Disease**
What is a common finding in Alz disease and how can it be corrected by drugs?
There is a general cholinergic deficiency in the brain, which the patient can be given AChE inhibitors to help.
