11-12 NeuroPATH Degenerative Diseases

Question 1

Alzheimer’s Dz: Clinical Presentation/Heritability

Answer 1

—usually >65 y/o
—short-term memory loss
—r/o all other possibilities
—usually no fam hx (if so, usu. means early presentation)

Question 2

AD: Anatomic Location?

Answer 2

cortex

Question 3

AD: Pathological Features

Answer 3

—gross: cortical ATROPHY of frontal, parietal, and temporal lobes (occipital spared); larger ventricles b/c atrophy
—histo: flame-shaped neurofibrillary TANGLES made of tau; βA-senile PLAQUES (neither pathgnomonic)

Question 4

AD: Molecular biology

Answer 4

—tau (a hyperphosphorylated microtubule binding protein) —> flame-shaped neurofibrillary tangles
—β-amyoloid: senile plaques
——β-AP cleaved from larger prot
——ApoE Removes messed up amyloid

Question 5

Huntington’s Dz: Clinical Presentation/Heritability

Answer 5

—always heritable (autosomal dom)
—chorea and dementia
—presents 30-50 y/o

Question 6

HD: Anatomic Location?

Answer 6

caudate

Question 7

HD: Pathological Features

Answer 7

degenerated caudate w/ asso’d increased size of the lateral ventricle (hydrocephalus ex vacuo)

Question 8

HD: Molecular biology

Answer 8

CAG tri-nuc repeat in huntingtin gene on 4p; longer repeat is assoc’d w/ earlier onset

Question 9

Parkinson’s Dz: Clinical Presentation/Heritability

Answer 9

—rarely familial
—resting, pill-rolling tremor
—bradykinesia
—rigidity
—usually not inherited

Question 10

PD: Anatomic Location?

Answer 10

midbrain

Question 11

PD: Pathological Features

Answer 11

GROSS: degen/depigmentation of SN and Locus Ceruleus
HISTO: Lewy bodies (synuclein) round cytoplasmic inclusion

Question 12

PD: Molecular biology

Answer 12

α-synucleinopathy

Question 13

Four Broad classes of neurodegenerative dzs (classified by protein)?

Answer 13

1> “tauopathies” with inclusions containing the microtubule associated protein tau
2> “synucleinopathies”, with synuclein-containing inclusions
3> a group with ubiquitin-containing inclusions that are not tau and not synuclein and whose molecular biology we are just beginning to understand
4> the trinucleotide repeat diseases, many but not all of which have proteins with abnormally expanded poly-glutamine repeats.

Question 14

Down’s Syndrome and AD

Answer 14

—βAPP gene is located on chromosome 21
—Downs pts develop memory loss beginning in their 30’s
—path looks like AD
—? caused by extra copy of the βAPP gene

Question 15

most common cause of dementia in geriatric pts?

Answer 15

AD by far

Question 16

Pick’s Dz gross appearance FYI

Answer 16

only fronto-temporal atrophy

Question 17

Pick’s Dz other FYI

Answer 17

“3R-tauopathy”

—“Pick cells” are large, swollen neurons seen in the affected cortex in Pick’s disease

Question 18

Corticobasilar dementia FYI

Answer 18

frontoparietal atrophy
—pt usu ~60 y/o
—with an asymmetrical clumsiness, stiffness, or jerking of an arm or more rarely of a leg. —2-3yrs—> rhythmic myoclonus
—“alien limb” (limb moves w/o vol ctrl w/ pt having feeling limb doesn’t belong to them)
—sensory disturbances
—now recognized as presenting in some patients with a frontotemporal dementia.
—ballooned neurons (basically the same thing as Pick cells) in the affected frontoparietal lobe and neuronal loss, microvacuolation, and astrocytosis.

Question 19

Progressive supranuclear palsy FYI

Answer 19

PSP is one of the tauopathies
—inclusions are globose tangles in regions of the basal ganglia, brainstem (including the oculomotor complex), and other areas.
—multisystem degeneration clinically characterized by Parkinsonism and supranuclear ophthalmoplegia.

Question 20

ALS

Answer 20

—5-10% familial
—spont. upper motor neuron degen (Betz cells and their axonal extensions in the corticospinal tracts) and lower motor neurons (anterior horn cells and cranial motor nerves)
—40-70 y/o
—relentlessly progressive 2-6 year course
—classical presentation:
—A) wasting (lower motor involvement) in the upper extremities
—B) spasticity/hyperreflexia (upper motor involvement) in the lower extremities.
—Sensation and intellectual functions preserved
—Death often results from respiratory failure due to involvement of the cervical cord.
—DX w/ muscle biopsy

Question 21

Friedrich’s Ataxia FYI

Answer 21

triad of sx:
1. hypoactive knee and ankle jerks
2. signs of progressive cerebellar dysfunction
3. preadolescent onset
—GAA repeat within frataxin gene (mito gene for Fe metab)