Neurodegenerative Disorders Flashcards
(152 cards)
1
Q
This disease is the most common cause of dementia
A
Alzheimer’s disease
2
Q
Alzheimer’s disease is due to accumulation of these two compounds
A
Tau and amyloid beta
3
Q
Does Alzheimer’s disease have plateaus?
A
NO
(ex: vascular dementia does)
4
Q
Does Alzheimer’s disease have acute/sudden or insidious/gradual onset?
A
Insidious/gradual
5
Q
This is the most dominant finding in Alzheimer’s disease
A
Memory loss
(recent memory >)
6
Q
Does Alzheimer’s disease have motor deficits early or late?
A
Late
7
Q
Alzheimer’s disease pathology is mainly in the cerebral cortex, with relative sparing of this
A
Occiput
8
Q
Patients with Alzheimer’s disease typically die within this many years of diagnosis
A
5 years
(death from pneumonia, other infection, inanition)
9
Q
Amyloid precursor protein is on this chromosome
A
21
10
Q
Pathogenesis of Alzheimer’s disease may involve abnormal degradation of this protein that’s encoded on chromosome 21
A
Amyloid precursor protein (APP)
11
Q
In normal individuals, amyloid precursor protein is cleaved by these two enzymes
A
Alpha secretase THEN gamma secretase
12
Q
In normal individuals, amyloid precursor protein is cleaved by alpha secretase then gamma secretase, into amino acid fragments of this size
A
40 amino acids
(are soluble)
13
Q
Are 40 or 42 amino acid fragments of amyloid beta soluble?
A
40
(42 are insoluble and produce amyloid deposits)
14
Q
In Alzheimer’s disease, amyloid precursor protein is cleaved by these enzymes
A
Beta secretase than gamma secretase
15
Q
In Alzheimer’s disease, amyloid precursor protein is cleaved by beta secretase then gamma secretase, forming amino acid fragments of this size
A
42 amino acids
(are insoluble and produce amyloid deposits)
16
Q
Amyloid precursor protein is normally cleaved by alpha secretase, then this enzyme
A
Gamma secretase
17
Q
In Alzheimer’s disease, Amyloid precursor protein is cleaved by this enzyme first, then gamma secretase
A
Beta secretase
18
Q
Does alpha or beta secretase cleave amyloid precursor protein (APP) first in Alzheimer’s disease?
A
Beta
19
Q
Polymers/aggregates of this protein form neuritic plaques in Alzheimer’s disease
A
Amyloid beta
20
Q
Deposition of aggregates of this protein can cause cerebral amyloid angiopathy
A
Beta amyloid
21
Q
Allele of Apolipoprotein E that is normal, homozygous in 60%
A
e3
22
Q
Allele of Apolipoprotein E that promotes amyloid beta formation and increases risk of Alzheimer’s disease
A
e4
23
Q
Allele of Apolipoprotein E that decreases rate of amyloid beta formation
A
e2
24
Q
Neuritic plaques have an amyloid core, with entrapped and disordered _____
A
neurites
25
Does the number of neuritic plaques correlate with Alzheimer's disease severity?
NO
26
Histochemical stain for amyloid
Congo red
27
Neuritic plaques are positive in this stain
congo red
28
Neurites are positive on this stain
Silver stain
29
Does the number of tangles correlate with degree of dementia in Alzheimer's disease?
YES
(contrast to plaques, which do not)
30
Do neuritic plaques or tangles correlate with Alzheimer's disease severity?
Tangles
31
Granulovacuolar degeneration and Hirono bodies (intracellular eosinophilic rods in hippocampus) are associated with this condition
Alzheimer's disease
(are not pathogenic)
32
Hirono bodies are associated with Alzheimer's disease, and are intracellular eosinophilic rods in this structure
Hippocampus
33
Widened sulci and narrow gyri are seen in this condition
Alzheimer's disease
34
This structure of the brain is most affected early in Alzheimer's disease
Hippocampus
35
What is the biggest risk factor for Alzheimer's disease?
Age
36
Being homozygous or heterozygous for Apoe4 allele is a risk factor for this condition
Alzheimer's disease
37
Being homozygous or heterozygous for this allele is a risk factor for Alzheimer's disease
Apoe4
38
Lack of this allele is a risk factor for Alzheimer's disease
Apoe2
39
Lack of apoe2 allele is a risk factor for this condition
Alzheimer's disease
40
Why is Down syndrome a risk factor for Alzheimer's disease?
Because it is trisomy 21, and amyloid precursor protein is encoded on chromosome 21
41
Apoe4 allele is on this chromosome
Chromosome 19
42
Mutations in this protein may cause gain of functions in gamma secretase (affects ratio of A beta 42:40, contributing to Alzheimer's disease)
Presenilin
43
Presenilin is a component of this enzyme
Gamma secretase
44
What is the best evidence for Alzheimer's disease?
Autopsy is best
45
A high ratio of phosphorylated to unphosphorylated Tau in CSF could indicate this condition
Alzheimer's disease
46
Reduced amyloid beta 40 in CSF could indicate this condition
Alzheimer's disease
47
In frontotemporal degeneration, do memory deficits occur early or late?
Late
(personality, behavioral, language deterioration first)
48
These are two types of inclusions that can be seen in Frontotemporal degeneration
FTLD-tau (hyperphosphorylated Tau inclusions)
FTLD-tdp42 (ubiquitinated TDP43 inclusions)
49
FTLD-tau (hyperphosphorylated Tau inclusions) and FTLD-tdp42 (ubiquitinated TDP43 inclusions) could be seen in this condition
Frontotemporal degeneration
50
Does identity of cellular inclusions correlate with pattern of disease expression in frontotemporal degeneration?
No
51
"Knife edge" atrophy of frontal and temporal lobes, with sparing of posterior superior temporal gyrus, is seen in this condition
Frontotemporal degeneration
52
What is the typical age of onset of Frontotemporal degeneration?
40-50's
53
A typically responsible and mild-mannered middle aged adult who has stopped showering and is using vulgar language may have this condition
Frontotemporal degeneration
54
Broca's or Wernicke's aphasia may occur with this neurodegenerative disorder
Frontotemporal degeneration
55
Does dementia occur early or late in Parkinson's disease?
Late
56
In Parkinson's disease, neuronal loss begins in this structure, then the substantia nigra and cortex
Brainstem
57
Is the D1 or D2 basal ganglia pathway underactive in Parkinson's disease?
D1
58
Aggregates of this form Lewy bodies
Alpha synuclein
59
Tremor at rest is characteristic of this condition
Parkinson's disease
60
Intention tremor occurs due to damage to this structure
Cerebellum
61
Does Parkinson's disease involve tremor at rest or intention tremor?
Tremor at rest
62
Does Parkinson's disease involve spasticity?
No
63
Festinating gait is characteristic of this condition
Parkinson's disease
64
A patient with micrographia, masked facies, reduced blinking and drooling may have this condition
Parkinson's disease
65
These two conditions will have Lewy bodies (alpha synuclein aggregates)
Lewy body dementia and Parkinson's disease
66
Does memory deficit or movement disorder occur first in Parkinson's disease?
Movement disorder
67
Does memory deficit or movement disorder occur first in Lewy body dementia?
Memory deficit
68
Cortical tracts are affected earlier in this neurodegenerative disorder characterized by early dementia
Lewy body dementia
69
Parkinsonism can be seen in Lewy body dementia, and is often exacerbated by this type of drug
Neuroleptics
(antipsychotics)
70
What is the key symptom that differentiates Lewy body dementia from Parkinson's disease?
Early dementia
(episodic dementia, especially nocturnal)
71
Episodic dementia, especially nocturnal, is characteristic of this condition
Lewy body dementia
(can also have hallucinations and paranoid delusions)
72
Parkinsonism disorder with prominent ocular and postural findings
Progressive Supranuclear Palsy
73
Neurodegenerative disorder characterized by disequilibrium with frequent falls, and vertical gaze palsy
Progressive Supranuclear Palsy
74
A patient with erect posture, wide-eyed stare, and frequent falls without explanation may have this neurodegenerative disorder
Progressive Supranuclear Palsy
75
Supranuclear ophthalmoplegia is seen in this neurodegenerative disorder
Patient can't look down often
Progressive Supranuclear Palsy
76
Progressive Supranuclear Palsy is a selective atrophy of this part of the brain
Midbrain
(superior colliculus, red nucleus, subthalamic, globus pallidus)
77
Progressive Supranuclear Palsy is a selective atrophy of midbrain, with sparing of this
Pons
78
Mouse Ears appearance on transverse view and Hummingbird on sagittal view MRI are seen in this condition
Progressive Supranuclear Palsy
79
Atrophic dorsal midbrain at superior colliculus, neurofibrillary tangles with Tau protein, and neuronal loss with gliosis are seen in this condition
Progressive Supranuclear Palsy
80
Alien limb sensation is characteristic of this atypical Parkinson syndrome
Corticobasal degeneration
81
This condition is similar to Progressive supranuclear palsy, but lesions are more concentrated on cortex and basal ganglia
Corticobasal degeneration
82
This condition begins with asymmetric motor abnormality, then eventually bilaterally
Frontal predominant dementia
Corticobasal degeneration
83
Is symmetric or asymmetric cortical atrophy seen in Corticobasal degeneration?
Asymmetric
84
Is unitlateral or bilateral basal ganglia atrophy seen in Corticobasal degeneration?
Bilateral
85
Multiple system atrophy is a degenerative disorder of these tracts
White matter
86
In Multiple system atrophy, SNCA gene mutation results in loss of these cells
Oligodendrocytes
87
Condition where a single nucleotide change in SNCA gene (for alpha synuclein) results in oligodendrocyte loss
Multiple system atrophy
88
SNCA gene encodes for this protein
Alpha synuclein
89
This gene encodes for alpha synuclein
SNCA
90
This gene is mutated in Multiple system atrophy
SNCA (alpha synuclein)
91
Parkinsonism condition that affects autonomic tracts
Multiple system atrophy
92
Multiple system atrophy involves neuronal and oligodendrocyte loss in these 3 systems
Striatonigral, Cerebellar, Autonomic
93
Hot cross bun sign on MRI is seen in this condition
Multiple system atrophy
94
These inclusions in oligodendrocytes are seen in Multiple system atrophy
Alpha synuclein
95
Alpha synuclein inclusions in oligodendrocytes are morphologically seen in this condition
Multiple system atrophy
96
Alpha synuclein inclusions in these cells are seen in Multiple system atrophy
Oligodendrocytes
97
Cortical hyperphosphorylated tau in perivascular distribution is seen in this condition
Chronic traumatic encephalopathy
98
Globose neurofibrillary tangles are seen in this Parkinsonism disease
Progressive supranuclear palsy
99
Lewy bodies in substantia nigra are seen in this condition
Parkinson's disease
100
Lewy bodies in cortex are seen in this condition
Lewy body dementia
101
Autonomic symptoms, especially orthostatic hypotension, are characteristic of this Parkinsonism disease
Multiple system atrophy
102
A patient with changes in mood and memory, and a history of trauma, will have this accumulation in the cortex, in a perivascular distribution
Hyperphosphorylated tau
(Chronic traumatic encephalopathy)
103
Is a progressive or stepwise decline seen in vascular dementia?
Step-wise
(classically due to multiple small infarcts)
104
Microinfarct and microbleeds can cause this type of dementia
Vascular dementia
105
CADASIL can cause this type of dementia
Vascular dementia
106
Binswanger's disease can cause this type of dementia
Vascular dementia
107
This disease is also known as subcortical arteriosclerotic encephalopathy
Binswanger's disease
108
Binswanger's disease involves a hypoperfusion of these areas
Subcortical and periventricular white matter
109
Binswanger's disease is associated with these 3 conditions
Hypertension
Cardiac disease
Diabetes type 2
110
Is white or gray matter affected in Binswanger's disease?
White
(is hypoperfused)
111
CADASIL (Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) involves a mutation in this gene
NOTCH3
112
Is CADASIL (Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) a degeneration of white or gray matter?
White
113
Vascular dementia without a history of hypertension or diabetes may be caused by this condition
CADASIL (Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy)
114
Vascular dementia in a patient with hypertension or diabetes may be caused by this condition
Binswanger's disease
115
CAG repeat in Huntingtin gene expands during this
Spermatogenesis
(causes genetic anticipation)
116
Neurons releasing this neurotransmitter in the caudate nucleus are lost in Huntington's disease
GABA
117
Marionette walking is characteristic of this condition that may also involve writhing and tongue rolling
Huntington's
118
Are there behavioral symptoms with Huntington's disease?
YES - especially depression
(also irritability, anxiety, impulsivity)
119
Does dementia occur with Huntington's disease?
Yes - subcortical dementia
(attention, concentration, motivation)
120
In Huntington's disease, this stain will be more positive
GFAP
(neuronal loss + astrocytic gliosis)
121
Are astrocytes seen in Huntington's disease?
Yes - astrocytic gliosis (GFAP +)
122
Decreased GABA neurons with astrocytic gliosis are seen in this condition
Huntington's disease
123
Friedreich ataxia and Ataxia-telangiectasia are two variants of this type of degeneration
Spinocerebellar degeneration
124
What is the inheritance pattern of Friedreich ataxia?
Autosomal recessive
125
Friedreich ataxia is due to a GAA trinucleotide expansion in this gene
Frataxin gene
126
In Friedreich ataxia, GAA trinucleotide expansion in frataxin gene leads to accumulation of this in mitochondria
Iron
(is neurotoxic)
127
In Friedreich ataxia, GAA trinucleotide expansion in frataxin gene leads to accumulation of iron in this organelle
Mitochondria
128
GAA trinucleotide expansion in frataxin gene occurs in this condition
Friedreich ataxia
129
Mitochondrial iron accumulation is seen in this condition
Friedreich ataxia
130
These three spinal tracts are most vulnerable to iron accumulation in Friedreich ataxia
Spinocerebellar (ataxia)
Corticospinal (UMN spastic paralysis)
Dorsal columns (loss of propiorception)
131
Lesion to this tract in Friedreich ataxia causes ataxia
Spinocerebellar
132
Lesion to this tract in Friedreich ataxia causes UMN spastic paralysis
Corticospinal
133
Lesion to this tract in Friedreich ataxia causes loss of position sense / proprioception
Dorsal columns
134
A child with staggering gait, kyphoscoliosis and cardiomyopathy may have this condition
Friedreich ataxia
135
Death occurs in adulthood with Friedreich ataxia due to this
Heart/restrictive lung disease
136
Neurodegenerative disorder with progressive ataxia that can cause diabetes mellitus
Friedreich ataxia
137
What is the inheritance pattern of Ataxia Telangiectasia?
Autosomal recessive
138
Ataxia Telangiectasia is due to a mutation in this
dsDNA repair enzyme
139
Condition involving cerebellar atrophy that is caused by disorder of dsDNA repair enzyme
Ataxia Telangiectasia
140
Sensitivity to ionizing radiation occurs with this spinocerebellar degeneration
Ataxia Telangiectasia
141
Immunodeficiency and lymphoid neoplasms are characteristic of this condition involving cerebellar atrophy
Ataxia Telangiectasia
142
Patients with Ataxia Telangiectasia often die at this age group
Teenage
143
This symptom of Ataxia Telangiectasia is seen in early childhood
Ataxia-dyskinesia
(due to cerebellar atrophy)
144
This symptom of Ataxia Telangiectasia occurs later in childhood
Ocular and cutaneous telangiectasias
145
Loss of upper and lower motor neurons are seen in this condition
Amyotrophic lateral sclerosis
146
Are upper or lower motor neurons lost in Amyotrophic lateral sclerosis?
Both
147
In Amyotrophic lateral sclerosis, there is atrophy of this brain structure
Precentral gyrus
148
Both Amyotrophic lateral sclerosis and Frontotemporal degeneration can have this type of inclusions
TDP43
149
Atrophy of precentral gyrus and neurons with TDP43 inclusions are seen in this condition
Amyotrophic lateral sclerosis
150
This condition often begins with asymmetric loss of fine motor skills
Can also have unilateral limb weakness, head drop, swallowing, speech difficulty
Amyotrophic lateral sclerosis
151
What usually causes death in Amyotrophic lateral sclerosis?
Respiratory compromise or infection
152
Neurons with these inclusions may be seen in Amyotrophic lateral sclerosis
TDP43
