Midterm 2 Flashcards
(229 cards)
1
Q
True or False: Dementia is not a normal part of growing old
A
True
2
Q
What is dementia characterized by?
A
Multiple cognitive deficits with memory impairment as a frequent early symptom
3
Q
What is the main difference between dementia and normal aging?
A
Dementia’s symptoms are more frequent where as normal aging is sometimes
4
Q
What is the cognitive decline in dementia?
A
Very sharp
5
Q
What can mild cognitive impairment (MCI) lead to?
A
Full blown dementia
6
Q
What is super aging?
A
Above normal aging, cognitive resilience
7
Q
What happens to the brain volume as we age?
A
Decrease of gray matter and changes in white matter
8
Q
What is the decrease in gray matter associated with?
A
Reductions in neuronal number and or volume
9
Q
What are the changes in white matter associated with?
A
Reductions in the diameter of myelin sheath
10
Q
What is synaptic plasticity?
A
The ability of synapses to strengthen or weaken in response to activity often associated with structural changes
11
Q
Where do age related changes in synapses and synaptic plasticity occur?
A
Gray matter
12
Q
What changes occur in the gray matter as we age?
A
Reductions of neurotransmitters, calcium dysregulation, mitochondrial dysfunction, oxidative stress
13
Q
What does demyelination in normal aging contribute to?
A
Age related memory changes (decrease in normal aging is normal
14
Q
Where does demyelination occur?
A
White matter
15
Q
What are examples of subtle cognitive decline in aging brains?
A
Slower reaction times
Lower attention levels
Slower processing speeds
Decreased sensory and perceptual function
Changes in sleep pattern
Increased training can improve the performance of aged individuals
16
Q
What are the factors that influence brain aging?
A
Genetics
Environment
8 hours of sleep per night (lack of sleep impacts normal aging or cognitive ability)
17
Q
What is neurogenesis?
A
The process by which neurons are generated from neural stem cell and progenitor cells
Responsible for populating the growing brain with neurons
18
Q
Where does neurogenesis occur?
A
Subventricular zone (SVZ) and Sub-granular zone (SGZ)
19
Q
What is the subventricular zone (SVZ)?
A
Lead new cells to repopulate olfactory bulb (OB)
20
Q
What is the sub-granular zone (SGZ)?
A
Lead new cells to repopulate the granular cell layer in dentate gyrus
21
Q
Where is the subventricular zone (SVZ)?
A
At the base of the ventricles
22
Q
Where is the sub-granular zone (SGZ)?
A
Around the granular layer
23
Q
What slows down neurogenesis?
A
Aging
24
Q
Where is neurogenesis restricted to in the adult human brain?
A
The hippocampus (sub-granular zone SGV) and the subventricular zone (SVZ)
25
What factors enhance neurogenesis?
Environmental enrichment (active conversation, reading, mental exercises)
Exercise
26
What factors decrease neurogenesis?
Neurodegenerative disease
Depression
Aging
27
What can you do to delay cognitive decline?
Minimize stress
Exercise
Networking (active social life)
Diet
Higher education (mental activity)
28
True or false: Exercise can prevent or delay dementia?
True
29
What can consistent exercise do?
Delay onset of symptoms
Improve arterial health
Alter brain chemistry
Improve mood
Slow cognitive decline
Causes changes in blood flow
30
What is parabiosis?
Anatomical joining of two individuals artificially in physiological research
31
What happens when young blood is mixed into old blood?
Young blood reverses age related impairments in cognitive function and synaptic plasticity
(young blood improves old subject cognitive performance)
32
What happens when old blood is mixed into young blood?
Negatively regulates neurogenesis and cognitive function
(old blood impairs young subjects performance)
33
True or false: Blood plasma from young donors show evidence of cognitive improvement
True
34
True or false: Caloric restrictions enhance aging and decreases cognitive performance
False
35
True or false: Alzheimer's disease causes dementia?
True, it is a major cause
36
What is dementia?
An umbrella term (symptom)
37
What are the symptoms of dementia?
Difficulties with everyday tasks
Confusion in familiar environments
Difficulty with words and numbers
Memory loss
Changes in mood and behavior
38
What is important to remember with dementia symptoms?
Some components/ symptoms come at different times
39
What are the two types of brain disorders?
Specific disorders (focal damage, restricted to a particular brain region)
Generalized disorders (widespread disorders, affects the whole brain)
40
What are specific disorders?
The disorder depends on the area of the brain affected (bullet wounds, strokes)
41
What are generalized disorders?
Affects multiple cognitive abilities (closed head injury, dementing disorders, demyelinating diseases, toxic substances)
42
What are neurogenerative disorders associated with?
A huge loss of gray matter or neurons
43
What are dementing diseases?
Loss of cognitive function, sometimes accompanied by personality changes, which interferes significantly with the individual's daily activities work and social activities
44
What are the three stages of dementing diseases?
Mild, moderate and severe
45
What is mild dementia?
Person retains judgement and can sustain daily activities on his/her own but work and social activities are impaired
46
What is moderate dementia?
Independent living becomes hazardous and requires some degree of supervision
47
What is severe dementia?
Cognitive abilities are so compromised that the person requires constant supervision (loss of self)
48
What is important to remember about the stages of dementia?
Not all patients have to go through all stages, might die before it gets worse
49
What is aphasia?
Loss of ability to understand or express speech
50
What is apraxia?
Inability to link skilled motor movements to ideas or representations
(Inability to use motor function to speak)
51
What is agnosia?
Deficit in recognizing objects that occurs in the absence of deficits in sensory processing
(Unable to identify objects or people)
52
What is acalculia?
The inability to perform simple mathematic calculations the patient previously knew
53
What are the types of clinical classifications of dementia?
Cortical, subcortical and mixed
54
What is cortical dementia?
Co-occurrence of many cognitive deficits including aphasia, apraxia, agnosia, acalculia, visuospatial deficits and memory problems (changes in cortical regions)
Ex. Alzheimer's, Frontotemporal dementias, Creutzfeldt-Jakob (prion diseases)
55
What is subcortical dementia?
More likely to manifest first as personality changes, attention deficits, slowness in cognitive processing, difficulties with tasks requiring strategy (In the subcortical areas)
Ex. Parkinson's, Huntington's
56
What is mixed dementia?
Both cortical and subcortical involvement, patters of cognitive performance midway between cortical and subcortical types (Memory and movement changes)
Ex. Vascular dementia, Lewy body dementia
57
What is the main difference between subcortical and cortical dementia?
Subcortical--> changes in posture and movement (no memory impairment)
Cortical--> memory impairment
58
How are dementias classified?
On the basis of their underlying pathologies, which are largely defined by accumulation of abnormal protein aggregates in neurons and glia, as well as in the extracellular compartment, in vulnerable regions of the brain
59
What are the six main categories of neurodegenerative proteinopathy that a vast majority of non vascular dementias fall into?
Amyloid-B (AB), microtubule- associated protein tau, TAR DNA-binding protein 43 (TDP-43), fused in sarcoma (FSU), a-synuclein, and prion protein
60
What are the 5 major diseases of dementia?
Alzheimer's disease (most common, mixed pathologies)
Vascular dementia
Dementia with lewy bodies
Frontotemporal dementia
Parkinson's disease (least common)
61
What are the symptoms of Alzheimer's Disease?
Impaired memory
Impairment in at least one other cognitive domain
Impairs social or occupational functioning
Gradual onset and continual decline
62
What is the pathology of AD?
Neurofibrillary tangles and amyloid plaque
63
What is the genetic associates with AD?
Can be influenced by genetics, but not always
64
What is the prevalence with AD?
Prevalence has increased over the years
Because population and life span has increased (reflection of demographic of the country)
65
What are the symptoms Frontotemporal Dementia (FTD)?
*Mostly behavioral changes*
No amnesia in early stages
Clinical syndrome-- associated with shrinkage of the frontal and temporal lobes
Impulsive or bored and listless
Inappropriate social behaviors
Neglect of personal hygiene
Repetitive or compulsive behavior
Speech problems, semantic deficits
66
What are the two branches of FTD?
Primary progressive aphasia and behavioral-variant frontotemporal dementia (bvFTD)
67
What is behavioral-variant frontotemporal dementia?
*Behavioral changes*
Changes in social conduct and behavior
Loss of empathy
Apathy
Disinhibition
Lack of insight
68
What is primary progressive aphasia?
Progressive disorder of language (language deficits)
69
What are the two branches of primary progressive aphasia?
Semantic dementia (SD) and progressive nonfluent aphasia (PNFA)
70
What is semantic dementia (SD)?
*Comprehension impaired*
Loss of semantic knowledge, impaired word comprehension and object naming
Fluent speech with spared repetition
71
What is progressive nonfluent aphasia (PNFA)?
*Speech impaired*
Apraxia and effortful speech
Spared object and word comprehension
72
What are Lewy bodies a mutation of?
alpha synuclein (a-synuclein)
73
What are the symptoms of Dementia with Lewy bodies?
Similar to AD in terms of cognitive features
Bradykinesia, rigidity(inability to be to bent or be forced out of shape)
Recurrent and well formed hallucinations
Impacts emotions
*memory deficits less severe than AD but visuospatial deficits are more severe than AD
74
What are the stages of the progression of Lewy body dementia
Early stages--> Delusions, restlessness, REM sleep disorder, movement difficulties, urinary issues
Middle stages-->Motor impairment, speech difficulty, decreased attention, paranoia, significant confusion
Later stages--> extreme muscle rigidity and speech difficulties, sensitivity to touch, susceptibility to infections
75
What is vascular dementia also known as?
Multi-Infract Dementia (MID)
76
What is vascular dementia caused by?
Blockages in the brains blood supply
Small strokes all over the brain
77
What is the relation between VD and AD
VD is the second most common form
May cause or exacerbate Alzheimer's
(Increases chances of having AD)
78
What is the cognitive profile of VD?
More impaired than AD patients on executive function
Less impaired on episodic memory
79
What are the risk factors that cause VD?
High blood pressure
Diabetes
High cholesterol
Family history of heart problems
Obesity
Smoking
80
What is Parkinson's disease?
Progressive neurologic disease
Changes in specifically substantia nigra with dopamine
81
What is the neuropathology of PD?
Degeneration of dopamine (DA) producing neurons in the brain (substantia nigra)
82
What are the motor symptoms of PD?
Tremors
Bradykinesia (slowness of movement and speed)
Rigidity
83
What are the neuropsychiatric symptoms of PD?
Executive dysfunction
Memory deficits
Attention deficits
Visuospatial deficits
Mood disturbances
Impulse control behaviors
84
What happens to the brain with AD?
Shrinkage of gray matter (loss of neurons)
Loss of white matter (loss of myelination)
Enlargement of lateral ventricles
85
What essential jobs of the brain does AD disrupt?
The ability for neurons to communicate with each other, carry out metabolism and repair themselves to stay healthy
86
What are amyloid plaques?
Insoluble extracellular deposits which accumulate in the cortex and hippocampus
Composed of amyloid-beta(AB) protein fragments: AB40 and AB42
87
What are neurofibrillary tangles?
Bundles of insoluble helical fibers within neurons
Composed of hyperphosphorylated tau proteins that are normally associated with microtubules
88
What happens with Alzheimer cells
Intensive loss of synaptic contacts and neurons
89
When do amyloid plaques form?
When there is an imbalance between accumulation and clearance of AB from the brain
90
Where are amyloid plaques found?
Outside the cell
91
Where are neurofibrillary tangles found?
Inside the cell, tau is a resident of neurons
92
What do tau proteins do to microtubules?
Tau proteins stabilize microtubules in neurons
93
What are microtubules main functions
Provide structure, organize the cytoplasm of the cell and serve as tracts for the transport of cellular elements form the cell body to the axonal terminals(synapses)
94
True or false: There are changes in microglia and astrocytes in AD
True
95
What does the activation of the immune system do to AD pathology?
Contributes to the pathogenesis of AD
Neuroinflammation
96
_______are beta-amyloid protein aggregates that form clusters of misfolded protein outside of the cell bodies
Plaques
97
Are plaques intercellular or intracellular?
Intercellular
98
Are tangles intercellular or intracellular?
Intracellular
99
True or false: All patients that have plaques in the brain have dementia?
False
100
True or false: All patients that have tau in their brain have dementia
True
101
What do PET scans of Alzheimer's patients reveal?
Reduced brain glucose metabolism
Reduced functionality in the brain
102
What do MRI scans of Alzheimer's patients reveal?
There is an increase of uptake in compounds (increase of plaque)
103
What are the risk factors for AD
Age, #1 risk factor
Genetics, mostly for early onset
ApoE4, genetic risk factor, however only a risk factor and does not mean that if you have it you will get the disease
Non-genetic factors: head trauma, high blood pressure, heart disease, stroke, diabetes and high cholesterol (not as high as genetic factors)
104
How can you prevent AD?
No evidence for prevention yet
Cognitive and psychosocial activities may reduce risk
Phase lll prevention trial: A4 Trial
2 new drugs used
105
True or false: Physical exercise can reduce the risk for AD
True
Aerobic and strength training show positive effects
106
What is Alzheimer's Disease?
Irreversible and progressive neurodegenerative disorder
107
What is Alzheimer's Disease characterized by?
Gradual loss of memory and other cognitive functions, deficits in activities of daily living, behavior, personality and judgement
108
What are the symptoms of AD?
Gradual loss of memory
Decline in ability to perform routine tasks
Disorientation
Difficulty in learning
Loss of language skills
Impairment of judgement and planning
Personality changes
109
True or false: The cost of Alzheimer's Disease is rising
True
110
True or false: The cause of death from Alzheimer's Disease is falling
False
111
Is the lifetime risk for AD greater for men or women?
Women
112
What age does people with AD affect the most?
65+
113
True or false: Funding for AD is plentiful
False
114
What are the 3 types of cognitive decline?
Preclinical, MCI and Dementia
115
What are the characteristics of preclinical cognitive decline?
Silent phase, brain changes without measurable symptoms
Individual may notice changes, but not detectable on tests
(Stage where the patient knows but the doctor doesn't)
116
What are the characteristics of MCI cognitive decline?
Cognitive changes are concern to individual or family
One or more cognitive domains impaired significantly
Preserved activities of daily living
117
What are the characteristics of dementia cognitive decline?
Cognitive impairment severe enough to interfere with everyday abilities
118
What are the three stages of Alzheimer's Disease progression?
Mild, moderate and severe
119
What are the characteristics of mild AD progression?
Loss of recent memory
Faculty judgement
Personality changes
120
What are the characteristics of moderate AD progression?
Verbal and physical aggression
Agitation
Wandering
Sleep disturbances
Delusions
121
What are the characteristics of severe AD progression?
Loss of all reasoning
Bedridden
Communication disability
122
What is Mild Cognitive Impairment (MCI)
Prodromal to AD (period between the appearance of initial symptoms and full development)
Memory complaint
Measurable, greater than normal memory impairment detected with standard memory assessment tests
123
What stays the same in MCI?
Normal general thinking and reasoning skills
Maintained ability to perform normal daily activities
124
What are the drugs used for behavioral changes in AD used for?
Agitation and or psychosis
Depression
Apathy
Sleep disturbances
125
What type of drug is used against AD?
Antibodies against amyloid
126
Why has it been difficult to find drugs against AD?
Because by the time it gets to mild to moderate dementia the disease has already progressed too much
127
What do tau molecules do in a stable microtubule?
Tau molecules normally bind to and stabilize microtubules
128
What happens when microtubules disintegrate?
Microtubules disintegrate because tau proteins form tangles clumps
129
What is tau phosphorylation?
Beta amyloid (Aβ) accumulates abnormally in the brain during AD, and this prompts tau to become hyperphosphorylated aggregation causes microtubules to fall apart
130
Is tau soluble or insoluable?
Highly soluble, does not form aggregates
131
Is hyperphosphorylated tau insoluble or soluble?
Hyperphosphorylated tau is insoluble and dysfunctional contributing to microtubule destabilization
132
What does hyperphosphorylated tau filaments cause?
Reverse neuronal dysfunction then neurodegeneration
133
What is tauopathy?
A class of neurodegenerative diseases that is associated with pathological aggregation of tau proteins in the brain
134
What are the two types of tauopathy?
Primary tauopathy and secondary tauopathy
135
What is primary tauopathy?
Diseases which have tau pathology as primary pathology
Ex. Chronic Traumatic encephalopathy and Frontotemporal Lobar Degeneration
136
What is secondary tauopathy?
Disease which have Tau pathology as well as other major pathologies
Ex. AD is a secondary tauopathy, it is also an amyloidosis-- aggregation of senile plaques (A-Beta plaques)
137
What is important to note about isoforms in the human brain?
Different diseases are associated with different isoforms
138
What isoform is expressed in the fetal human brain?
Only 0N3R Tau is expressed
139
What are the 5 diseases under tauopathy classification?
Frontotemporal dementia (Picks Disease)
Corticobasal degeneration (CBD)
Progressive supranuclear palsy (PSP)
Chronic traumatic encephalopathy (CTE)
Alzheimer's Disease (AD)
140
What is tauopathy a disease of?
A disease of 3R or 4R
141
What is Chronic Traumatic Encephalopathy?
Progressive degenerative disease occurring in those with multiple concussions and head injuries
(Usually found in athletes)
Tau becomes free when concussions happen
Prone to development of AD from repeated injuries
142
What does the brain look like in CTE?
Enlargement of ventricles
Holes in hippocampus, from degeneration
Memory impairment
143
What are the pathological features of CTE?
Tau deposition as neurofibrillary tangles
Changes in white matter
Glial degeneration
Beta-amyloid deposition is uncommon
PET scans pick up both amyloid and tau
Very preliminary (precedes disease)
144
What is the major function of tau protein in normal healthy neurons?
Stabilizing microtubules
145
What are the three subtypes of Frontotemporal Disease (FTD)?
Progressive non-fluent aphasia (affects frontal lobe first)
Semantic dementia (affects left anterior temporal lobe first)
Behavioral variant Frontotemporal dementia (affects right frontal lobe first)
146
What is the common feature of the three subtypes of FTD?
All have progressive decline in frontal and temporal lobes
147
What is progressive non-fluent aphasia (PNFA)?
Starts focally in the left side of the frontal lobe
Broca's area primarily affected (speech production)
Hesitant effortful speech, speech apraxia, stutter, anomia,
phonemic paraphasia, agrammatism
As the disease develops, speech quantity decreases and many patients will become mute
148
What is semantic dementia?
Start in the anterior temporal lobes (more left than right)
Loss of semantic knowledge (loss of word meanings)
Starts with word finding problems
Some have a dramatic increase of visual creativity
149
What is behavioral variant FTD (BVFTD)?
Begins in the frontal lobes
Orbitofrontal cortex: involved in emotional processing
Right sided damage first: social behavioral impairments
Loss of the anterior cingulate, which is critical for motivational behaviors and conflict resolution
150
What are the symptoms of BVFTD?
Onset can be as early as 20s
Deficits in emotional processing
Deficits in behavioral and moral reasoning
Rather dramatic change early on in the disease
Inappropriate behaviors in public
Compulsive behaviors
Regression to child like state of reasoning
Very difficult to diagnose
151
What is the genetic relation to FTD?
40% of people with FTD have a family history of FTD or another related dementia
5-10% of patients have a family history that shows an autosomal dominant inheritance patter (if one parent has it, the offspring will have a 50% chance of having it)
5 genetic mutations linked to FTD
Symptoms and pathology vary depending on specific mutation and inheritance pattern
152
What proteins are associated with FTD?
TDP-43, FUS and Tau
153
What is the second most common neurodegenerative disease after AD?
Parkinson's Disease
154
What are the motor symptoms of PD?
Tremors, stiffness, impaired balance, bradykinesia, vocal symptoms
155
What are the neuropsychiatric symptoms of PD?
Depression, hallucinations, dementia
156
What form of PD is 90% of cases?
Sporadic
157
What form of PD is 5-10% of cases?
Familial (genetic)
158
True or false: All neurogenerative diseases in this class have a cure
False
159
What is the most crucial part of PD?
Fine motor skills degenerated
160
What are the nonmotor skill symptoms of PD?
Mental/behavioral issues, sense of smell, sweating and melanoma, gastrointestinal issues, pain in knees
161
What does young onset of PD mean(<40 years old)?
Most likely genetic form
162
What is PD characterized by?
Neurodegenerative disorder
163
What is does PD primarily affect?
Neurons in the substantia nigra
(Degeneration of substantia nigra)
164
What happens with neurons in PD?
Loss of neurons that produce dopamine
70% loss of neurons before symptoms
Dopaminergic neurons are selectively vulnerable to degeneration in PD
165
What does dopamine do?
Sends messages to the part of the brain that controls movement and coordination
166
What drug is used in response to the reduction of dopamine?
FDOPA
167
What are the functions of dopamine in the brain?
Behavior and cognition
Voluntary movement
Motivation
Punishment and reward
Working memory and learning
Sleep, mood and attention
168
True or false: There are Lewy bodies in substantia nigra in PD
True
169
What does aggregated alpha-synuclein form?
Lewy bodies
170
True or false: A-synuclein is toxic to dopaminergic neurons
True
171
What are mutated forms of A-synuclein prone to?
Misfolding and aggregation
172
What are the genetic mutations associated with PD?
DJ-1 (antioxidant/sensor of oxidative stress)
Parkin (Loss of function mutations, lead to mitochondrial dysfunction and oxidative stress)
Pink1 (Loss of function mutations, involved in proteasomal and mitochondrial function)
SNCA, a-synuclein (aggregation may disrupt proteasomal and mitochondrial function, mutations enhance a-syn aggregation
173
What 2 critical cellular functions do genetic mutations in PD affect?
Mitochondria or proteasomes
174
What are the therapeutic approaches for PD?
L-dopa: immediate precursor to dopamine
L-deprenyl: inhibitor of MAO-B, an enzyme that degrades dopamine
Invasive (surgical) approach: deep brain stimulation
Mitochondrial/antioxidant-based treatments
Synuclein-based therapies- vaccination, compounds that inhibit aggregation
Cell transplants- stem cells
175
What kind of disorder is Huntington's Disease?
Autosomal dominant genetic disorder
176
What does autosomal dominant?
One mutant copy of the gene is enough to cause disease
An affected person has a 50% chance of passing on the disease
177
What is polyglutamine disease (HD is one of several)?
Expansion of the CAG trinucleotide repeat encoding the amino acid and glutamine (Q)
178
What are the initial signs of HD?
Personality changes
Irritability
Depression
Small involuntary movements
Abnormal eye movements
Chorea
Trouble learning
179
What are the later signs of HD?
Progressive dementia
Dysarthria (loss of motor control of speech)
Choreoathetosis(chorea and twisting)
Rigidity
Wasting
180
What is the life expectancy of HD?
In adulthood: 15-20 years
In childhood: 10-15 years
181
What causes HD?
Neurodegeneration in basal ganglia
Medium spiny neurons (MSN)
182
Where does HD start in the brain?
Striatum
183
How is HD diagnosed?
Genetic test
Physical exam
Family history
184
What gene causes HD?
HTT gene provides instructions for making protein called huntingtin
185
What is the function of HTT?
Function unknown, appears to play an important role in neurons and is essential for normal development
May be involved with chemical signaling, transporting materials, attaching to proteins and other structures and protecting the cell from self destruction
186
What does the expanded CAG segment lead to?
The production of an abnormally long version of HTT
187
Why is elongated to HTT toxic?
Elongated HTT is cut into smaller, toxic fragments that bind together and accumulate in neurons, disrupting the neuron's normal functions
188
What does the cutting of elongated HTT affect?
Affects regions of the brain that coordinate movement and control thinking and emotions (striatum and cerebral cortex)
189
True or false: The dysfunction and eventual death of neurons in these areas of the brain underlie the signs and symptoms of AD
True
190
What number of CAG repeats is unaffected?
6-34
191
What number of CAG repeats is intermediate (premutation)?
35-39
192
What number of CAG repeats is mutant (pathogenic)?
40+
193
What happens as the mutant HTT gene is passed from one generation to the next?
The size of the CAG trinucleotide repeat often increases in size
194
What is the larger number of repeats associated with?
An earlier onset of the disease (anticipation)
195
What are the characteristics of the brain regions affected in adult onset of HD?
40-60 CAG repeats
Progressive pathology
First affects striatum
196
What are the characteristics of the brain regions affected in juvenile onset of HD?
>60 CAG repeats
Widespread pathology (not one particular region)
197
Where is huntingtin localized in?
The cytoplasm
198
What do mutated forms of huntingtin form?
Abnormal deposits called "inclusion bodies"
199
Where do inclusion bodies form?
In the nucleus, cytoplasm and dendrites
200
True or false: The longer the poly-Q, the more aggregation of HTT
True
201
What are the current palliative therapies of HD aimed at reducing?
Involuntary motor movements
Psychiatric symptoms (depression, anxiety, irritability, aggression, psychosis)
Supportive therapy (speech, physical)
Gene therapy trial
202
What are genetic neurodegenerative and neurodevelopmental diseases caused by?
Expansion of nucleotide repeats
203
Which disease is transmissable?
Prion disease of transmissible spongiform encephalopathies (TSE)
204
What is prion diseases or TSE?
A family of rare progressive neurodegenerative disorders that affect both animals and humans
205
What is Prion diseases or TSE distinguished by?
Long incubation periods, characteristic spongiform changes associated with neuronal loss and a failure to induce inflammatory response
206
What is the causative agent of TSE?
Prions
207
What are normal prions called?
PrPc
208
What are mutated/ misfolded prions?
PrPsc
209
How do prions multiply?
Nucleation and fragmentation
210
What is the difference between transmissible and infectious?
Transmissible can spread through neurons
Infectious needs to have a living pathogen(virus or bug)
211
True or false: Not all transmissible diseases are infectious but all infectious diseases are transmissible
True
212
What happens when prions propagate?
Normal proteins become misfolded then misfolds other proteins
213
How do pathological proteins transmit between cells?
They pass through the synapse
Seeds go to neighboring neurons
214
What does the normal function of prion (PrPc) do?
Located at pre and post synaptic sites where it regulates ion channels and neurotransmitter receptor functions
Helps maintain the myelin sheath
Role in memory and sleep
LTP and sleep patterns altered
215
True or false: Prions are transmissible
True
216
Prion diseases are caused by:
Infectious proteins
217
What are the diseases in human TSE?
Creutzfeldt-Jakob disease (CJD)
Kuru
Fatal Familial Insomnia (FFI)
218
What are the diseases in animal TSE?
Scrapie in sheep
Bovine Spongiform Encephalopathy (BSE), mad cow disease
Chronic Wasting Disease (CWD)
219
What are the subtypes of TSE?
10-15%- genetic (mutation in PrPc protein)
80-95%- sporadic
Rare- acquired
220
What is CJD?
Very rare-- can be sporadic, acquired or familial
Very rapid progression and deterioration of cognitive function once the symptoms appear
Caused by: prions
220
What are the characteristics of CJD?
Highly transmissible
Highly resistant to inactivation
Difficult to establish disease origin (sporadic)
Main inherited diseases prion disease are the genetic form of CJD, GSS and FFI
221
What are the symptoms of CJD?
Involuntary movements
Fatigue
Anxiety
Difficulty concentrating
Problems sleeping
Lack of coordination
Impaired gait
Altered vision
Pattern in EEG
Changes in MRI
222
What is the neuropathology of prion diseases?
Widespread loss in the cortex and proliferation of glial cells
Brain appears spongy, holes
223
True or false: There is a treatment to prion disease?
False, no known treatment
224
What are the prion diseases in animals?
Bovine Spongiform Encephalopathy(BSE) or mad cow disease
Scrapie
Chronic Wasting Disease (CWD)
225
What is BSE or mad cow disease?
Affects cattle
Caused by feeding cattle with food containing meat and bone from infected cattle and sheep
Can cross the animal-human barrier
226
What is scrapie?
Affects goats and sheep
Can't cross animal-human barrier
227
What is Chronic Wasting Disease (CWD)?
Affects cervids(deer, elk, moose)
Spreads through animal to animal contact and infected material such as soil
Can't cross animal-human barrier
228
True or false: We can vaccinate against animal prion diseases
False
