11-12 NeuroPATH Degenerative Diseases Flashcards
1) The clinical presentation of the disease. 2) The pathologic features of the disease. 3) The molecular biology of the disease.
Alzheimer’s Dz: Clinical Presentation/Heritability
—usually >65 y/o
—short-term memory loss
—r/o all other possibilities
—usually no fam hx (if so, usu. means early presentation)
AD: Anatomic Location?
cortex
AD: Pathological Features
—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)
AD: Molecular biology
—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
Huntington’s Dz: Clinical Presentation/Heritability
—always heritable (autosomal dom)
—chorea and dementia
—presents 30-50 y/o
HD: Anatomic Location?
caudate
HD: Pathological Features
degenerated caudate w/ asso’d increased size of the lateral ventricle (hydrocephalus ex vacuo)
HD: Molecular biology
CAG tri-nuc repeat in huntingtin gene on 4p; longer repeat is assoc’d w/ earlier onset
Parkinson’s Dz: Clinical Presentation/Heritability
—rarely familial —resting, pill-rolling tremor —bradykinesia —rigidity —usually not inherited
PD: Anatomic Location?
midbrain
PD: Pathological Features
GROSS: degen/depigmentation of SN and Locus Ceruleus
HISTO: Lewy bodies (synuclein) round cytoplasmic inclusion
PD: Molecular biology
α-synucleinopathy
Four Broad classes of neurodegenerative dzs (classified by protein)?
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.
Down’s Syndrome and AD
—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
most common cause of dementia in geriatric pts?
AD by far
Pick’s Dz gross appearance FYI
only fronto-temporal atrophy
Pick’s Dz other FYI
“3R-tauopathy”
—“Pick cells” are large, swollen neurons seen in the affected cortex in Pick’s disease
Corticobasilar dementia FYI
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.
Progressive supranuclear palsy FYI
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.
ALS
—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
Friedrich’s Ataxia FYI
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)
