6.4.2 Neurodegenerative Diseases Flashcards
What is the white arrow pointing at?
Lewy body in substania nigra
What is the main type of deposit in FTLDs?
Tau deposits
Prior to death, this patient demonstrated signs of dementia. What is the most likely cause of this patient’s dementia?
DLB (not Alz Dz because there is no cortical atrophy)
DLB often has a normal brain weight with little to no atrophy
What is the most common genetic cause of ALS?
C9orf72- intronic hexanucleotide expansion (open frame mutation)
What is the most common neurodegenerative dz behind Alz Dz?
Dementia with Lewy bodies (DLB)
What are the two primary protein aggregates in AD?
Beta-amyloid plaques (extracellular)
Phosphorylated tau tangles and threads (intracellular)
What are major degenerative disorders that cause adult dementia?
Alzheimer disease, Dementia with Lewy bodies, Frontotemporal lobar dementia (Pick dz)
What are the main clinical features of a patient with Parkinson dz?
resting tremor, bradykinesia (or akinesia), rigidity that may be initially unilateral but progressees to involve both sides
Which lobes of the brain are primarily affected by AD? Which lobe of the brain is typically preserved?
Atrophy prominent in temporal pole, medial temporal lobe (amygdala and hippocampus), frontal and partietal lobes
Preserved: Occipital lobe
What type of proteinopathy are these conditions?
What is the common thread between protein aggregates that lead to disease?
The native protein structure is lost, and fibrils form and accumulate
What are some genes that have been linked to Alz Dz?
APP, PS1, PS2, ApoE4
What are some of the genetic loci that have been identified in AD or AR inherited Parkinson dz?
LRRK2, gene for alpha-synuclein
Name this condition. What is the importance of fluorescence on Thioflavin S staining?
AD; Fluorescence confirms beta-pleated sheet conformation of protein aggregate
What is the black arrow pointing at? What protein comprises that aggregate?
Lewy body; alpha-synuclein
In DLB: Lewy bodies accumulate in brain stem, pons, limbic areas, neocortex
Which protein aggregate found in AD correlates better with dementia?
Tau “tangles” (ptau)
Diagnose him
Parkinson Dz
What intracellular inclusion is being stained in these slides?
Tau neurofibrillary tangles
Name this condition
Pick dz (FTLD-tau)
What is the neuropathology and the affected areas of ALS?
How can Parkinson Dz be distinguished from other extrapyramidal movement disorders at autopsy?
Presence of lewy bodies in the surviving neurons of the brainstem
What disease? What is shown in these images?
Parkinson dz
1st 2 images: substantia nigra compacta cell loss, loss of striatal dopamine content
3rd image: Lewy body
What are the main clinical features of frontal temporal lobar degeneration (FTLD)?
Progressive language deterioration and personality changes
Describe these conditions [ALS, Alz dz, Parkinson dz, dementia with lewy bodies (DLB), FTLD (pick dz)] as either cerebral cortical disorders or motor pathway disorders.
Pick bodies and Pick cells
Severe neuronal loss in outer cortical layers
Pick cells are swollen pale neurons (ballooned neurons)
Name two alpha-synucleinopathies.
Dementia with lewy bodies (dementia
Parkinson Dz (movement disorder)
What are the clinical features of DLB?
Progressive dementia with flucuations in coginition and arrousal
REM sleep behavior disorder
Visual halLEWYnations
Variable mild parkinsonism
What pathologic feature of AD are the red arrows pointing at? Why does this occur?
Hydrocephalus ex vacuo: occurs in response to atrophy of the cerebral lobes, not as a result of excessive CSF production
Name the type of dz
FTLD
What type of protein is tau>
Axonal microtubule-associated protein (MAP)
Name this condition
Alzheimer Disease
What type of aggregates can be found in motor neurons of ALS patients?
TDP-43
What gene is associated with Alzheimer disease because of its role in processing of amyloid precursor proteins? Chromosome?
APP gene on chromosome 21
What neurotransmitter is decreased in the cortex of a patient with AD?
Ach
