Neurodegenerative Disease Flashcards
What is aphasia?
Loss of ability to understand or express speech
What is apraxia?
Inability to form words- motor dysfunction of speech
What is agnosia?
Inability to interpret sensations and recognize things
Name 6 common treatable causes of dementia
- Stroke
- Infections (CJD, Syphilis, HIV)
- Neoplasms
- Drugs (barbiturates, alcohol, heavy metals)
- Metabolic (hypothyroidism, liver disease)
- Vitamin deficiencies (cobalamin, thiamine, niacin)
Alzheimer’s disease primarily affects what part of the brain?
Cerebral cortex
Lewy body disease primarily affects what part of the brain?
Cerebral cortex
Pick’s disease primarily affects what part of the brain?
Cerebral cortex
Idiopathic Parkinson’s primarily affects what part of the brain?
Basal ganglia
Huntington’s disease primarily affects what part of the brain?
Basal ganglia
Multiple system atrophy affects what part of the CNS?
Cerebellum and spinal cord
ALS affects what part of the CNS?
Cerebellum and spinal cord
Spinal muscular atrophy affects what part of the CNS?
spinal cord
Frederich’s ataxia affects what part of the CNS?
Cerebellum and spinal cord
What is the most common neurodegenerative cause of senile dementia?
Alzheimer’s disease
What percent of Alzheimer’s cases are early onset (familial)?
10%
What is the inheritance pattern of Alzheimer’s?
Autosomal Dominant
What is the pathogenesis of familial alzheimers?
Deposition of amyloid protein
Spitting of what protein leads to amyloid protein?
Amyloid precursor protein (APP) located on chromosome 21
What do Down’s patients develop alzheimer’s earlier?
They have an extra copy of 21 and therefore more APP. They tend to get alzheimer’s earlier on (40’s and 50’s)
What is the role of presenilin 1 and 2 in alzheimers?
They split the APP to form amyloid
What is the role of ApoE4 and ApoE2 in alzheimers?
ApoE4 is correlated with higher incidence of alzheiers
ApoE2 is correlated with lower incidence of alzheimers
APP is normally cleaved by _____ to form Abeta protein?
Alpha-secretase
Mutated APP is cleaved by ______ to form A beta peptide, which deposits as amyloid in alzheimers
beta-secretase
How does the gross appearance of a brain with alzheimers appear?
Significant cortical atrophy
Dilated ventricles (hydrocephalus ex vacuo)
atrophied hippocampus
What is the characteristic microscopic findings of alzheimers disease?
Neurofibrillary tangles
Are neurofibrillary tangles intra or extracellular?
Intracellular
What are neurofibrillary tangles composed of?
hyperphosphorylated Tau proteins (tau- normal intermediate filament protein)
Are amyloid plaques intra or extracellular?
Extracellular
What is the stain used to visualize amyloid plaques?
Bielschowsky silver
What does amyloid angiopathy have to do with alzheimers disease?
Amyloid angiopathy is present in variable degrees in nearly all AD cases.
It is the same amyloid found in senile plaques
What is amyloid angiopathy
Amyloid deposition in the walls of arterial vessels in the subarachnoid space and superficial cortex
What is the second most common type of neurodegenerative dementia?
Lewy Body Disease
WHat is the clinical progression of Lewy Body Disease?
Early dementia with visual hallucinations followed by parkinsonian symptoms
WHat is the composition of lewy bodies?
alpha-synuclein
Where are lewy bodies found in the CNS?
Cortex and brainstem
What is the third most common cause of neurodegenerative diseases?
The group of diseases known as Frontotemporal lobar degeneration
What are clinical symptoms associated with frontotemporal lobar degeneration?
Change in personal and social conduct. –> often associated with disinhibition and language changes
The majority of frontotemporal lobar diseases are linked to mutations in what protein? Located on what chromosome?
Tau proteins - located on chromosome 17
Other than Tau protein, name two other proteins mutated in frontotemporal lobar diseases
Ubiquitin
TDP-43 protein
What is the presenting feature of Pick’s disease?
Aphasia (loss of ability to express or understand speech)
What is the classic findings on histologic sections of someone with PIck’s disease?
PIck bodies
What do Pick bodies look like?
Round and basophilic
What are pick bodies composed of?
Tau
Where in teh CNS are pick bodies found?
Hippocampus and cortex
List the three features that clinically define Parkinson’s DIsease
Fluctuating cognition
Visual hallucinations
Features of parkinsonism: rigidity, bradykinesia , stooped posture, masked facies, shuffling gait, resting tremor
Name the histological feature seen in Parkinson’s
Lewy Bodies- composed of alpha- synuclein
What is the appearance of the substantia nigra in someone with Parkinson’s Disease?
Pale- there is atrophy of the substantia nigra
What is the inheritance pattern of Huntington’s Disease?
Autosomal Dominant with anticipation
What is the genetic problem seen in Huntington’s Disease? Which chromosome?
Abnormal expansion in CAG triplet repeat on chromosome 4
What are 2 clinical features of Huntington’s Disease?
Choreiform movements
Psychiatric symptoms progressing to dementia and cachexia
Decreased levels of which two neurotransmitters are seen in Huntington’s?
GABA and ACh
What causes neuronal death in Huntington’s?
NMDR-R binding and glutamate toxicity
Which two parts of the basal ganglia are damaged/atrophy in Huntington’s?
Caudate and putamen- (the dorsal striatum)
What are the main symptoms of Multiple System Atrophy?
Symptoms consist of variable combination of parkinsonism, cerebellar ataxia, and autonomic dysfunction – depend on the neuronal system involved.
What is the pathology of Multiple System Atrophy (what types of inclusions are seen)?
Glial cytoplasmic Inclusions- composed of alpha-synuclein
Coronal brain sections of someone with multiple system atrophy of which part of the basal ganglia?
Putamen
Outside of the cerebrum, what 4 other parts of the brain can show atrophy in someone with multiple system atrophy?
Cerebellum, substantia nigra, pons and olivary nucleus
What is the gene associated with familial ALS?
SOD-1 on chromosome 21
5-10% of cases are sporadic
Describe the appearance of the ventral and dorsal roots in someone with ALS
Ventral roots: severely atrophied due to destruction of descending efferent motor neurons (both UMNs and LMNs are affected)
Dorsal roots: normal appearing. Sensory is not impaired in ALS
What is the inheritance pattern of Werdnig-Hoffmann Disease?
Autosomal recessive
Which cells are affected by Werdnig-Hoffmann disease (SMA I)?
anterior horn cells –> LMN problems –> neurogenic atrophy of distal muscles
Differentiate Spinal Muscle Atrophy types I, II and III
SMA I- Werdnig-Hoffmann Disease “Floppy baby syndrome”
SMA II- Occurs at 3 months or later- slow progressive course with normal life span
SMA III- onset anywhere between infancy and adolescence. Very rare
All spinal motor atrophy disease (SMA’s I-III) are caused by mutations in what?
Survival of Motor Neuron genes (SMN1, SMN2) on chromosome 5
What is the most common form of hereditary ataxia?
Friedrich’s Ataxia
What is the inheritance pattern of Friedreich’s ataxia?
Autosomal Recessive
What is the gene mutated in Friedreich’s ataxia?
Trinucleotide repeat (GAA) - glutamic acid - in the FRATAXIN gene on chromosome 9
What is the role of frataxin?
Regulation of mitochondrial iron
What causes the ataxia in friedreich’s ataxia?
Degeneration of the cerebellum
What is the most common cause of death for someone with Friedrich’s Ataxia?
Cardiac causes- in addition to degeneration of different spinal cord tracts, there are electrical conductance and structural anomalies that lead to death
Which spinal tracts are destroyed in Friedreich’s ataxia?
Posterior columns, spinocerebellar columns, and corticospinal tract
+ atrophy of dorsal roots,
Name the three Tau-opathies
Alzheimer’s, Pick’s disease, some FTLD’s
Name the three poly gluatamine diseases
Huntington’s Disease
Spinocerebellar ataxia
Friedreich’s ataxia
Name the three alpha-synucleinopathies
Parkinson’s Disease
Lewy Body Disease
Multiple Systems Atrophy
Name a TDP43-opathy
one of the FTLD
What is mixed dementia?
Alzheimer’s disease + vascular dementia
Vascular amyloidosis increases the risk of developing what?
Hemorrhagic Strokes
What is vascular dementia
Vascular dementia is a decline in thinking skills caused by conditions that block or reduce blood flow to the brain, depriving brain cells of vital oxygen and nutrients
What are pathological findings associated with vascular dementia?
Multiple strokes, or a single stroke in a strategic site (thalamus, angular gyrus, ACA territory)
Small vessel disease
What causes Wernicke’s syndrome?
Thiamine deficiency
What 4 areas of the brain are primarily affected by alcohol toxicity?
- Wernicke’s area (due to thiamine deficiency)
- Central pontine myelinolysis
- Cortical atrophy
- Atrophy of the cerebellar vermis
What is the triad of WErnicke’s encephalopathy?
Oculomotor abnormalities (ophthalmoplegia, nystagmus)
Cerebellar dysfunction
Altered Mental status
What is Korsakoff’s psychosis?
Loss of recent memory compensated by confabulation
What area of the brain is damaged leading to the symptoms of Wernicke’s encephalopathy?
Mammillary body
-it becomes hemorrhagic and atrophic
