Chapter 20 - Neurodegeneration

Question 1

Clinical features of Parkinson’s

Answer 1

resting tremor, difficulty in initiating movement (akinesia), slowing of movement in general (bradykinesia), less movement of facial muscles, rigidity in the joints, mostly motor related

Question 2

Areas of the brain affected in Parkinson’s

Answer 2

Substantia nigra, basal ganglia

Question 3

Cellular pathology of parkinson’s

Answer 3

loss of dopaminergic neurons in substantia nigra

Question 4

known/potential causes of parkinson’s

Answer 4

no definitive cause

Question 5

current treatments for parkinson’s

Answer 5

Levodopa (L-DOPA), a metabolite of tyrosine, the immediate precursor of DA (can cross BBB and convert to DA)
Other treatments aimed at increasing DA signaling in the brain
Pharmacological treatments for PD are primarily symptomatic,
not disease altering

Question 6

Clinical features of Alzheimer’s

Answer 6

Begins insidiously, progresses gradually from forgetfulness and cognitive impairment, to physical problems, loss of communication skills, anhedonia, depression and withdrawal, and psychotic delusions and hallucinations

Question 7

Areas of the brain affected in Alzheimer’s

Answer 7

Amyloid plaques and neurofibrillary tangles result in cell degeneration, especially in the frontotemporal association cortex

Question 8

cellular pathology of Alzheimer’s

Answer 8

accumulation of beta-amyloid protein (β-amyloid, or A-beta [Aβ]) between neurons
In early stages neurofibrillary tangles (NFTs) are found in the entorhinal cortex, with progression to the hippocampus and neocortex

Question 9

known/potential causes of Alzheimer’s

Answer 9

Advancing age, family history, obesity, untreated hypertension, high cholesterol, stress, sedentary lifestyle, head trauma or hypoxic brain injury, depression, bipolar disorder, PTSD

Question 10

Genetic component of Alzheimer’s

Answer 10

Genes for (amyloid precursor protein) APP, on chromosome 21
Presenilin-1 (PS-1), on chromosome 14
Presenilin-2 (PS-2), on chromosome 1

Question 11

treatments for alzheimer’s

Answer 11

Cholinesterase inhibitors: improve cognition by increasing ACh in the synapse
NMDA glutamate receptor antagonist memantine (Namenda) prevents excitotoxic neuron damage
Antibodies against phosphorylated tau proteins
Chemotherapy drugs that reduced tangles in mice
Spin-labeled fluorene compounds reduce plaque formation in cultures
Antibiotic treatments; tied to relationship between the gut microbiome and neuroinflammation

Question 12

Clinical features of Huntington’s

Answer 12

Motor and cognitive symptoms result from degenerative effects on the basal ganglia, involuntary movement jerky or writhing, e rigidity, dystonia, problems with speech and swallowing, gait
problems, higher order thinking, and perserveration

Question 13

Known cause of Huntington’s

Answer 13

A trinucleotide repeat (a CAG sequence) results in a gain-of-function mutation in the Huntington gene (HTT)
Likelihood of developing HD depends on the number of CAG repeats in the gene; complete penetrance at 40 repeats

Question 14

current treatments for huntington’s

Answer 14

none can alter the course, Tetrabenazine (Xenazine) decreases the excessive movements, DA antagonist drugs, anticonvulsants, anxiolytic drugs, and antidepressants

Question 15

clinical features of Amyotrophic lateral sclerosis (ALS)

Answer 15

Degeneration of spinal motor neurons manifests as tripping, clumsiness, dropping things, abnormal muscle fatigue.
Or it may begin with difficulty in chewing and swallowing and facial weakness, slurred speech

Question 16

cellular pathology of ALS

Answer 16

Motor neurons show disruption of the cytoskeleton and aggregates of neurofilaments with other proteins to form “spheroids”

Question 17

genetic factors of ALS

Answer 17

about 10% of cases are familial

Question 18

potential causes of ALS

Answer 18

exposure to chemicals such as insecticides and pesticides

Question 19

treatment for ALS

Answer 19

Riluzole (Rilutek) – presynaptic inhibitor of glutamate release; thought to provide benefit by blocking glutamate-mediated excitotoxicity
Edaravone (Radicava) - prevents oxidative stress damage to neurons
Botulinum toxin minimizes sialorrhea (excessive salivation and drooling)
Dextromethorphan HBR and quinidine sulfate (Nuedexta) for PBA

Question 20

Clinical features of Multiple sclerosis (MS)

Answer 20

Fatigue, numbness/tingling
Walking/balance/coordination problems
Bladder and/or bowel dysfunction; sexual dysfunction
Vision problems, dizziness and vertigo
Cognitive dysfunction, emotional changes
Spasticity

Question 21

areas of the brain affected in MS

Answer 21

autoimmune disorder; result of chronic attack on the myelin produced by oligodendrocytes in the brain, spinal cord, and optic nerves

Question 22

how to diagnose MS

Answer 22

One must have lesions in at least two distinct areas of the CNS or
optic nerves
Or combinations of lesions, symptoms, CSF oligoclonal bands, or
progression of disease

Question 23

potential/known causes of MS

Answer 23

Risk is greater in people who live above 40° latitude in the Northern Hemisphere up to the age of 15
- Protective vitamin D may be a factor
Environmental toxins and infections such as measles may increase risk
There seems to be some genetic component

Question 24

treatments for MS

Answer 24

Treatments may be disease modifying or intended to treat an acute exacerbation, or to treat specific symptoms
Other treatments include monoclonal antibodies and chemotherapy drugs, to suppress elements of the immune system