Aula 10 - Neurodegenerative Diseases Flashcards
(21 cards)
What is dementia?
Syndrome characterised by general cognitive
decline, affecting memory, navigation, language, affects, motivation, reasoning, behavioural and/or motor domains that interfere significantly with a person’s ability to maintain their activities of daily living.
What are the four main types of dementia? Briefly distinguish them.
- Alzheimer’s Disease: characterized by the accumulation of beta amyloid plaques and tau tangles in the brain.
- Vascular Dementia: characterized by injury or disease in the blood vessels that decrease blood flow to the brain.
- Frontotemporal Dementia: characterized progressive degeneration of the frontal and temporal lobes in the brain.
- Lewy Body Dementia: characterized by the accumulation of Lewy bodies (clumps of protein) in the brain.
Lewy Body Dementia is usually associated with another neurodegenerative disease. Which one?
Parkinson’s Disease
What is type of dementia is mainly confused with Alzheimer’s? How can we distinguish them solely based on the patient’s symptoms?
Frontotemporal dementia is often confused with Alzheimer’s. But:
* Alzheimer’s usually presents 1st) as memory changes and 2nd) as behavioral changes.
* Frontotemporal dementia usually presents 1st) as behavioral changes and 2nd) as memory changes.
Neurodegenerative diseases are multifactorial. What are the three main factors envolved in the development of these diseases?
- Inflammation
- Mitochondrial dysfunction
- Oxidative stress
What are the two main types of Alzheimer’s Disease?
- Early Onset Alzheimer’s Disease (< 65 years old) - 5% of cases
- Late Onset Alzheimer’s Disease (> 65 years old) - 95% of cases
What are the main genes associated with Early Onset Alzheimer’s Disease?
- PSEN1 and PSEN2 (Presenilins)
- APP (Amyloid Precursor Proteins)
What is the role of PSEN1 and PSEN2 in Early Onset AD?
Presenilin 1 (PSEN1) and presenilin 2 (PSEN2) genes encode the major component of y-secretase, which is responsible for sequential proteolytic cleavages of amyloid precursor proteins and the subsequent formation of amyloid-β peptides.
What is the role of APP in Early Onset AD?
Amyloid Precursor Proteins (APP) are transmembrane proteins, mostly found near the synapses of neurons. Their role is to help neurons grow and repair after an injury. Like other proteins, APPs are used, broken down and recycled. APPs are normally cut by two enzymes, 𝛼-secretase and 𝛾-secretase. The resulting peptides are soluble and are eliminated. However, if instead of 𝛼-secretase, another enzyme called 𝛽-secretase cuts APPs together with 𝛾-secretase, it leads to the formation of ammyloid-β peptides.
What is the main gene associated with Late Onset Alzheimer’s Disease?
Apolipoprotein E (Apo-E): a protein involved in lipid metabolism in the brain that is associated with Alzheimer’s disease.
What are the two main AD hallmark signs that accumulate in the brain?
Amyloid plaques and tau (or neurofibrillary) tangles.
Amyloid plaques are found ________ (inside/outside) neurons and neurofibrillary tangles are found ________ (inside/outside) neurons.
outside, inside
How are amyloid plaques formed?
Amyloid Precursor Proteins (APP), which are mostly found near neuron synapses, are normally broken down by two enzymes: 𝛼-secretase and 𝛾-secretase. The resulting peptides are soluble and are eliminated. However, if instead of 𝛼-secretase, another enzyme called 𝛽-secretase cuts APPs together with 𝛾-secretase, the resulting peptides, which are monomers called amyloid beta, are insoluble and can easily bond together outside the neurons, forming beta-amyloid plaques. These plaques can build-up between neurons, disrupting the communication between them and affecting brain function, and even causing damage and inflammation.
How are neurofibrillary tangles (or tau tangles) formed?
The tau protein is an essential protein in neurons, playing a crucial role in the stability of microtubules, the structures that make up the neuronal cytoskeleton. Beta-amyloid plaques can initiate pathways inside the neuron that lead to the activation of kinase, an enzyme that transfers a phosphate group to the tau protein. As a result, tau proteins change shape, stop supporting the microtubules and clump up with each other, forming neurofibrillary tangles. Neurons with tangles are dysfunctional and undergo apoptosis, leading to neuron death.
How can Alzheimer’s be definitively diagnosed?
After death, through a brain autopsy.
What are the three main AD biomarkers found in the Cerebral Spinal Fluid (CSF)?
- Aβ42 (amyloid β 42)
- p-Tau (phosphorylated tau)
- t-Tau (total tau)
What are the two main imaging techniques used to diagnose Alzheimer’s?
MRI and PET
What are the main brain areas affected by Alzheimer’s?
What are the main imaging patterns of Alzheimer’s found in MRI?
- mesial temporal lobe atrophy (particularly the hippocampus, entorhinal cortex and perirhinal cortex)
- temporoparietal cortical atrophy
Name some protective factors against Alzheimer’s Disease.
- physical activity
- balanced diet
- maintaining a cognitive reserve
What is the name of the questionnaire that is usually done to detect cognitive impairment?
MMSE (Mini-Mental State Examination)
