Week 6.5 Flashcards
What is the protein aggregate found in AD, PD, HD, CJD, and ALS?
- AD: beta-amyloid, tau tangles
- PD: alpha-synuclein
- HD: huntingtin
- CJD: prion
- ALS: TDP-43
Alzheimer’s has a typical onset of what age?
sixty years old
Describe the gross pathology of Alzheimer’s disease.
- early medial temporal atrophy
- occipital lobe relatively spared
- large ventricles and hydrocephalus ex vacuo
Alzheimer’s typically spares what lobe of the brain?
occipital
What vascular disease is associated with Alzheimer’s disease?
cerebral beta-amyloid angiopathy
What are Hirano bodies?
actin aggregates common in the hippocampal neurons of those with Alzheimer’s
Beta-amyloid is a product of what metabolic process?
cleavage of the APP protein by beta- and gamma-secretase
The APP gene is located on which chromosome?
21
Down’s syndrome patients often suffer from early onset of what dementia?
Alzheimer’s
A functional tau protein plays what physiologic role?
it stabilizes microtubules
Which protein aggregate is more strongly associated with the onset of symptoms in Alzheimer’s?
the appearance of tau tangles
Tau tangles preferentially affect which brain regions?
- amygdala
- hippocampus
- lateral geniculate nucleus
What causes tau to become pathological?
it is phosphorylated
What are some genetic risk factors for Alzheimer’s disease?
presenilin-1 and ApoE4
The ApoE gene encodes a protein that does what?
it is a cholesterol transporter apolipoprotein
What is donepezil?
a centrally acting reversible AChE inhibitor that works to treat those with Alzheimer’s disease
Which NT system is affected in those with Alzheimer’s?
reduced acetylcholine
Name two drugs commonly used to treat Alzheimer’s.
- donepezil (AChE inhibitor)
- memantine (NMDA antagonist)
Lewy Bodies are a feature of what two disease?
Parkinson’s and dementia with Lewy Bodies
What are the symptoms of Dementia with Lewy Bodies?
- progressive dementia with fluctuations
- REM sleep disorder
- visual hallucinations
- variable parkinsonism
Lewy bodies are comprised of what protein?
alpha-synuclein
What genetic risk factor exists for dementia with levy bodies?
ApoE4
Autosomal dominant parkinson’s diseases is the result of a mutation in which gene?
leucine rich repeat kinase 2
Sporadic parkinson’s has been linked to mutations in which gene?
glucocerebrosidase
Frontotemporal lobar dementias share what features?
- progressive language deterioration
- personality changes
- atrophy of temporal and frontal lobes with sparing of parietal and occipital
Pick’s diseases is characterized by what protein aggregate?
tauopathy
Pick’s disease has an onset of when?
20-60 years of age
What are the symptoms of Pick’s disease?
- personality change
- loss of motivation
- lack of empathy
- inappropriate behavior
- language disturbance
- lack of insight
What is the most common genetic cause of ALS?
C9orf72
What protein aggregate is the hallmark of ALS?
TDP-43
What is the normal function of TDP-43?
work with FUS to ensure the long-term survival of motor neurons
What white mater tract is most affected by ALS?
anterior and lateral corticospinal tracts
