BIO T8 Flashcards
Which of the following is not a pharmacological treatment for Alzheimer’s disease?
a) Donepezil
b) Memantine
c) Rivastigmine
d) Metformin
D
Which class of drugs is commonly prescribed to alleviate symptoms of Alzheimer’s disease?
a) Antidepressants
b) Antipsychotics
c) Cholinesterase inhibitors
d) Anxiolytics
C
Which medication is an NMDA receptor antagonist used in the treatment of moderate to severe Alzheimer’s disease?
a) Donepezil
b) Rivastigmine
c) Memantine
d) Galantamine
C
What is the primary mechanism of action of cholinesterase inhibitors in Alzheimer’s disease treatment?
a) Blocking glutamate receptors
b) Enhancing cholinergic neurotransmission
c) Inhibiting serotonin reuptake
d) Increasing dopamine levels
B
Which of the following drugs is typically prescribed to manage behavioral symptoms such as agitation and aggression in Alzheimer’s patients?
a) Rivastigmine
b) Galantamine
c) Haloperidol
d) Memantine
C
What is the primary goal of combining Donepezil and Memantine in the treatment of Alzheimer’s disease?
a) To delay disease progression and improve cognitive function.
b) To reduce behavioral symptoms and agitation.
c) To prevent the formation of amyloid plaques in the brain.
d) To enhance neurogenesis and synaptic plasticity.
a
- Which stage of Alzheimer’s disease is typically targeted by the combination therapy of Donepezil and Memantine?
a) Mild cognitive impairment (MCI)
b) Early-stage Alzheimer’s disease
c) Moderate to severe Alzheimer’s disease
d) Advanced dementia
C
What is the ratio of glia and neurons?
Glia (etym. Glue of neurons old) outnumber neurons in the cerebral cortex, but neurons outnumber glia in several other brain areas (cerebellum)
Why is A-beta bad?
Misfolds and becomes sticky → clumbs to form oligemers → plaquesTrigger the release of cytokines because they’re observed by microglia → neural damage + synapse removal (phagocytosis)
What is the effect of oligimers
Weaken synaptic communication → might affect memory
What is neurodegeneration caused by Tau?
Tau (components of tangles) usually stablising the cytoskeletal transport → modified → abnormal shape + disconnected from the axon and moves towards the cell body → can spread to healthy neurons spreading tau’s malformation and neurodegeneration
What exactly causes the neural degeneration
excessive amounts of Amyloid beta in the cytoplasm of cells, not the external amyloid beta plaques → cytokines activated
Which chromosone has implicated in the production o amyloid beta?
21 chromosomes because people with down syndrome also have amyloid beta;
Under which conditions can amyloid-beta reproduce (Eisele et al., 2019)
After being boiled, steel still has hints of a-beta that can reproduce; even small scale
What is the amyloid beta hypothesis and related issues?
Extracellular a-beta accumulation triggers all pathological processes that culminate in AD → drugs targeting the secretase enzymes are not safe or effective
What is the Tau hypothesis and related issues?
Microtubule protein that causes neurodegeneration via breaking down axons and synaptic communication → effective treatments are challenging because of the complex AD pathology
What is the inflammation hypothesis and related issues?
Microglia + astrocytes → cytokines: using biomakerker treatments are complicated because they could interfere with the normal immune response
What is the cholinergic and oxidative stress hypothesis and related issues?*
Neuronal damage as a result of choline loss which uses acetylcholine → ACh esterase as symptomatic treatment but oxidative stress elevating components cannot be chemically bound to ACh-es
What is are new treatments suggested for AD?
Gut microbiome + Immune systemintestinal mucosal lymphoid tissue 70% - 80% of all immune cells in the body + first defence mechanismsCould also directly induce cytokine reaction, via GABA or via enteroendocrine cells that affect the brain through neuroimmune pathwaysCan affect neurotransmitter production and release (vagus nerve)
What is frontotemporal dementia?
= pick’s disease → genetic mutation that only causes NFTs and results in degeneration
of the frontal and temporal cortex → emotional changes and loss of executive functions (damaged prefrontal cortex), language disturbance (temporal lobe)
Explain the steps of AD pathogenesis?
Amyloid plaques extracellular beta-amyloid + degenerating axons and dendritesactivated microglia and reactive astrocytes, –> neuroinflammatory response produces cytokinesdestroy the degenerating axons and dendrites = only a core of beta-amyloid + neurofibrillary tangles consist of dying neurons that contain intracellular accumulations of twisted filaments of hyperphospholated tau protein –> leaves a trail of deformed and useless axons*
Which enzyme is responsible for what in AD?
a gene encodes the production of the ~-amyloid precursor protein (APP), a chain of approx imately 700 amino acids. APP i then cut apmt in two places by enzymes known as secretases to produce AP. TI, e first, P-secretase, cuts the ‘‘tail” off of an APP molecule. The second, y-secretase (gamma-secretase), cuts the “head” off. The result is a molec ule of AP that contains either 40 or 42 amino acids. The location of the second cut of the APP molecule by y-secretase determines which form is produced. In healthy brains, 90-95 percent of the Al3 molecules are of the short form; the other 5-10 percent are of the long form. In patients with Alzheimer’s disease the proportion of long Al3
Which brain region are affected by the neurodegeneration and how does an AD brain look?
the hippocampus entorhinal cortexneocortex (especially the association cortex of the frontal and temporal lobes)nucleus basalis locus coeruleus raphe nuclei
What is the other prevalence of AD?
10 percent of the population above the age of 6550 percent of people older than 85.
What is the prevalence of lewy bodies?
→ earlier framed in the context of parkinson’s now with dementia20% dementia diagnoses
Mild to moderate AD treatments?
Cholineesterase inhibitorsImmunotherapies (lecanemab, aducanumab via IV): a-beta in early stage AD slowed rate of cognitive decline vs. reduced a-beta plaques (amyloid-related imaging abnormalities = ARIA)*
Moderate to severe AD treatments?
N–methyl-D-aspartate (NMDA) antagonist → later stage regulates glutamate
What are side effects of cholinesterase inhibitors?
nausea, vomiting, diarrhea, insomnia, muscle cramps, fatigue, and weight loss., muscle weakness, dizziness
What are side effects of immunotherapeutic drugs?
ARIA, , headache, dizziness, falls, diarrhea, and confusion, cough, nausea, vomiting, fever, chills, body aches, fatigue, high blood pressure, low blood pressure, and low oxygen.
What are side effects of N–methyl-D-aspartate antagonistic drugs?
dizziness, headache, diarrhea, constipation, and confusion
Whata are side effects of combination treatments?
headache, nausea, vomiting, diarrhea, dizziness, anorexia, and ecchymosis (small bruising from leaking blood vessels)
Which medication cannot be taken by AD patients?
Sleep aids, anti-anxiety, anticonvulsants, antipsychoti
Which of the following could cause an increase in the amyloid path and, therefore, the formation of plaques?
Increased beta-secretase
How many people are affected by Parkinson’s disease?
1 to 2 percent of people over age 65 most prevalent movement disorder
What is the pathology of Parkinson’s disease?
Increasing loss of dopamine-releasing axons from the substantia nigra to the striatum → striatum decreases inhibition of globus pallidus → globus pallidus increases inhibition to the thalamus→ Damage in substantia nigra <img></img>
What are risk factors and causes of pd?
28 genes, toxin exposure, heroin knock-off containing MPTP → MPP+ which accumulates and destroys dopaminergic neurons by disturbing the pathway → mimicking symptoms, insecticides, herbicides, fungicides
What are the symptoms of Parkinson’s disease?
- Muscle tremors
- Rigidity
- Slow movements
- Loss of spontaneous movement (akinesia)
- Disturbances of posture
- Depression
- Dementia
- Sleep problems
- Difficulty in smelling
- Lack of motivation and pleasure
- Cognitive deficits (attention, memory, language)
When is the onset of Parkinson’s?
50s and 60s but symptoms years before
What further complicates the pathology?
Imparirment of dopaminergic transmission → more glutamatergic transmission → unbalanced striata (controls output of the basal ganglia) → overactive GABA output
What are lewy bodies?
cytoplasmic aggregates that accumulate and contain misfolded and ggregated alpha synuclein proteins
Which treatment might alleviate the symptoms of Parkinson’s?
NMDA antagonist if Parkinsons-’s conceptualised as a glutamate hyperactivity disorder?
Which three components have to be shown to lead to Parkinson’s in animal models?
6-OHDA → nigral DA neurons think it’s DA → selective destroction of monoaminergic cells → ipsilateral symptomsMPTPSpontaneous genetic mutation → weaver rat DA degeneration over month
What is meant by grafting?
Implanting a part of a brain tissue Intracerebral granting has been shown to be effective for cell replacement → DA release in the sriatum
How did they think that L-dopa can treat Parkinson’s?
L-dopa (pre-dopamine) crosses the blood-brain-barrier → increases dopamine release in axons, also deteriorated ones, but not other depleted neurotransmitters; nausea, restlessness, sleep problems, low blood pressure, repetitive movements, and sometimes hallucinations and delusions
What are other ways to treat Parkinson’s?
- Brain tissue transplant? Tough
- Stem cells? Also complicated
- Neurotrophins induce via surgery?
- Inserting electrodes to stimulate the brain: helps interrupt irregular firing
- Other dopaminergic drugs that haven’t been successful
- In what ways is L-dopa treatment disappointing?
L-dopa increases dopamine activity in spurts and in all neurons, not steadily and not just in those that need help. It does not stop the loss of neurons.
What procedure has improved the effectiveness of brain grafts for the treatment of Parkinson’s disease?
Results improved somewhat after physicians began giving drugs to suppress the immune response.
How do Alzheimer’s and cancer and the blood-brain barrier relate?
Capillary walls are weakenedTreatment molecules cannot pass
Which brain region is important for the implicit memory?
the striatum
* Parkinson’s patients (degeneration of neurons in the substantia nigra that project to the striatum) → Difficulty in learning habits
* Patients with Huntington’s disease(degeneration of several areas but in particular the striatum) → Difficulty in learning tasks in which a motor response is associated with a stimulus.
Which brain regions deteriorate with AD?
- Severe degeneration of the hippocampus, entorhinalcortex, neocortex (especially the association cortex ofthe frontal and temporal lobes), nucleus basalis, locuscoeruleus, and raphe nuclei* <img></img>
Which neurons are among the first to be affected in PD?
dopaminergic neurons in substantia nigra- because of Lewy bodies (deposits of alpha-synuclein protein)<img></img>
Levodopa chemical decomposition?
<img></img>
Why is l-dopa often combined with carbi dopa?
Carbidopa prevents levodopa from being broken down before it reaches the brain<img></img>
Which treatments are used for PD?
- Dopamine agonists
- MAO inhibitors
- COMT inhibitors
- Anticholinergics
- deep brain stimulation
- Pluripotent stem cells (PSCs) vs ventral mesencephalon tissue as a cell source for transplantation in Parkinson´s disease
How does a substantia nigra of a PD patient and a normal person look?
How does the substantia nigra of a Huntigton’s patient and a normal person look?
What are the symptoms of AD?
- Short-term memory loss
- Reading problems
- Pooer object recognition
- Pooer direction sense
- Poor judgment
- Impulsivity
- Short attention
- Visual problems
