Flashcards in lecture 10 - - Neurodegnerative disease, Vascular Dementia, and Prion Disease Deck (19):
Prion Disease --
Which is the most common form?
Biochemistry of the disease
1-2 cases per Million per years
Three forms: Familial, Sporadic, transmitted
Most common: Sporadic
Biochem: PRPC protein --> PRPSC which forms abnormal beta sheets resistant to proteases
Two human forms of prion disease and associated pathology?
Cruetzfeldt Jakob Disease --
Variant Form CJD
Variant CJD -- how is it acquired ?
Spongiform Degeneration of the gray matter with vaculoization --
Rapidly progressive (median survival 3.5 months) of dementia and startle myoclonus
Variant CJD -- thought be acquired through contaminated beef
What are the synucleinopathies ?
Multiple System Atrophy
What are the Tauopathies ?
what other disease?
Fronto-Temporal Dementia (Pick's Disease, FTDP-17)
PSP -- Progressive Supranuclear Palsy
(ALZ -- tangles = tau; senile plaques = beta)
what is vascular dementia?
what are the three subtypes
Vascular dementia -- Brain injury from vascular insufficeincy/ischemia/HTN
Step wise progression rather than gradual decline
Multiple Infarct Dementia
how is a dx typically conducted?
Cerebral Autosomal Dominant Angiopathy w/ Subcortical Infarcts and Leukoencephalopathy
(CVD and white matter damage)
Molecular -- Notch 3 Mutation
Sclerotic Changes, which can also be present on the skin (therefore skin bx is taken for Dx)
white matter degeneration secondary to vascular disease (small artery sclerosis)
Tau Tangles; Beta Amyloid Senile Plaques
Imaging: Ventricular englargement with Sulcal Widening
Pathogensis: ApoE4 increased risk for development;
Mutated genes for Presnelin 1 and 2 -- involved in metabolism of Beta Amyloid
Plaques = A-Beta Fragement of the Beta Amyloid
Tx - Increased ACH
Cholinesterase Inhibitors --
NMDA Antagonist -- Memantine (neuroprotective)
What are parkinsonisms?
Gross Path -- loss of pigment of the SN
Micropath -- Lewy Bodies in the SN
Loss of dopaminergic neurons
Parkinsonism -- Bradykinesia, Unilateral tremor, ridigity
Treatments: LevoDopa with dopamine metabolizing enzyme inhibitor (Carbidopa)
Other treatments -- MAOIs (block dopamine reuptake); COMT inhibitors; Dopamine Agonists
Lewy Body Dementia --
how does it differ from PD
Clinical onset for LBD: dementia first, then parkinsonisms
PD: Parkinsonism first
Multiple System Atrophy --
what 3 regions are damaged and how does the damage manifest
where does the synulcein accumulate?
SN -- dopamine loss = Parkisonisms
Olivopontocerebellar damage = ataxia
Preganglionic Neuron Autonomic Loss = Shy drager autonomic loss
Synuclein accumulates in oligodendrocytes (not neurons like PD)
Fronto temporal dementia (Picks and FTD-Parkinsonism Chr 17)
Progressive Supranuclear Palsy
What are the Frontotemporal Dementias --
how do they manifest ?
Pick's and FTDP_Chr17
Language dysfunction, personality changes, memory loss , dementia
Pick's Disease --
Tau positive Pick bodies; ballooned neurons
Progressive Supranuclear Palsy --
Vertical gaze ophthalamoplegia + Parkinsonism
Alien Limb Phenomena + Parkinsonisms + Alien Limb
damage to what?
UMN and LMN damage
Etiology -- idiopathic
Minority associated with mutation to SOD1
Characterisitc path -- Bunina bodies and TDP43 Inclusions