Forty Seven Flashcards
List 4 locations of neurodegeneration and what symptoms will result?
Cortex=dementia
basal ganglia=extrapyramidal symptoms/chorea
cerebellum/spine=ataxia
striatonigral pathway=parkinsons
What is the gene associated with the sporadic form of AD? Which form makes it high risk? lowers risk? When does it usually occur?
ApoE-Epsilon 4 leads to high risk. epsilon 2 is low risk.
Incidence increases at age 60
Which genes are associated with the familial form of AD? Which chromosome is the main one on?
Amyloid precursor protein (APP), on chromosome 21 (DS)
Presenelin 1 and 2
What are 3 steps in the pathogenesis of AD? Explain/give examples of each.
- Cholinergic system degeneration
- Neuronal loss in main source of cholinergic innervation for the hippocampus and neocortex (nucleus basalis of Meynert, diagonal band of Broca, medial septal nucleus) - Abnormal aggregates of altered proteins:
- Amyloid precursor protein (APP), Tau - Synaptic loss-first sign to occur, tough to see
What gross findings are there in AD?
Global cerebral atrophy (smaller gyri/larger sulci, lower brain weight, larger ventricles)
What are 4 things seen microscropically with AD?
ῆ Neuronal loss
ῆ Neurofibrillary tangles
ῆ Neuritic (senile) plaques
ῆ Congophilic amyloid angiopathy
What are some clinical signs of AD?
Clinically: − Dementia
− Recent memory loss − Spatial disorientation
− Personality changes − Paranoia
− Patient immobile, mute
Describe neuritic (senile) plaques? What protein are they made up of? What is the precursor to that protein? Where are they located?
ῆ Extracellular
ῆ Spherical collections of abnormal neuritis, microglia, astrocytes and AMYLOID core
A peptides ( beta-amyloid protein ) cleaved from
precursor protein APP
Describe neurofibrillary tangles. What is their shape? What protein are they compose of? Where are they located?
Intracellular
(intraneuronal)
“flame shaped ” cytoplasmic inclusion
ῆ Contain paired helical
filaments formed by
abnormally
phosphorylated tau
protein
ῆ Biochemically insoluble
What is congophillic angiopathy? What is it related to? What might it cause? What is it associated with/not associated with/exclusive to? What stain allows it to be seen better?
ῆ Amyloid (beta amyloid)
deposits in vessels walls
ῆ Not associated to
systemic amyloid
ῆ Can cause intracerebral
lobar hemorrhage
ῆ NOT exclusive for
Alzheimer, can be
sporadic
Congo red stain with polarized light.
What is the second most common cause of dementia? How does it happen? What does it look like microscopically?
Second most common
cause of dementia
ῆ Secondary to multifocal
infarcts often involving
subcortical and
strategically important
brain areas
ῆ Associate to
hypertension (hyaline
arteriolosclerosis),
atherosclerosis or
vasculitis
What are the clinical signs of Pick’s disease? What is the peak age? Where is the neurodegeneration? What happens there? What inclusions are there in this disease? What protein are they composed of? What do they look like microscopically? Where are they located?
ῆ Disinhibited behavior
and dementia
ῆ Peak age: 60 years
ῆ Circumscribed
involvement of FRONTAL and TEMPORAL lobes
ῆ Severe neuronal loss
ῆ Pick ’s bodies: TAU
inclusions: round,
cytoplasmic inclusion
Where does neurodegeneration occur in Parkinson’s disease? What inclusions do the neurons have? What do they look like? Where are they located? What is their main protein component?
- Nigrostriatal pathway degeneration
- Loss of dopaminergic input to corpus striatum - Neuronal loss in pigmented brainstem nuclei:
- Substantia nigra
- Locus ceruleus
- Dorsal vagal nuclei
ῆ Lewy bodies:
INTRANEURONAL , round
glassy and eosinophilic
cytoplasmic inclusion
ῆ Lewy body main
component is alpha-
synuclein
ῆ Lewy bodies are also
seen in Dementia with
Lewy bodies
What is the inheritance pattern of HD? When is the onset? What is the associated gene like? What nucleotides are involved? What is the gross pathology like?
ῆ Autosomal dominant
ῆ Onset between 25-45 years
ῆ Progressive deterioration and death in about 15 years from onset
ῆ Chorea, mood disturbances, dementia
ῆ A trinucleotide repeat
disease
ῆ Normal HD gene: 11-
34 copies of CAG
repeats
ῆ > 40 CAG copies =
Huntington ’s disease
and carrier
ῆ Atrophy of caudate nucleus
ῆ Flat ventricular wall (instead of convex)
What is the onset of amyotrophic lateral sclerosis? What are the symptoms? What is the prognosis ? What is the inheritance pattern? What gene is involved? What is the pathogenesis/where is? Where does atrophy occur?
ῆ 400 new cases each year (USA)
ῆ Onset in 6 th decade
ῆ Gradually progressive weakness
ῆ Death usually after 2-3years, respiratory failure
and aspiration pneumonia
ῆ 5 % familial
ῆ Some familial cases due to mutations in Cu/Zn superoxide dismutase(SOD1) gene.
ῆ Pathogenesis: Loss of upper motor neurons (cerebral
cortex) and/or lower motor neurons (cranial nerve nuclei, anterior horn cells)
ῆ Atrophy of motor cortex,ventral nerve roots and skeletal muscle (variable pattern)
