degenerative diseases Flashcards by Deja Gause

these are diseases of _ matter

there is a progressive loss of _ with assoicated secondary changes in white matter tracts

gray

neurons

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degernative diseases have protein aggregates that are resistant to degredation and are recognized histologically as _

inclusions

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dementia

progressive loss of congitive function INDEPENDENT of the state of attention

NOT apartof normal aging and is also pathologic

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_ is the most common cause of dementia in the elderly

Alzheimers disease

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Alzhemier disease is insidious impairement of _ _ functions with alreration in mood and behavior

(AD)

higher intelectual

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late clinical course of AD

disorientation, memory loss, aphasia

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5-10 years in AD

diables, mute, immobile

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AD is rarely symptomatic before the age of _

incidence rises with age and roughly double every _ years

5 years

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most cases of AD are _

_ examination is necessary and definitve for the diagnosis of AD

sporadic

pathological

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in AD there is global _ atrophy

there is widening of the _ mostly in the frontal, temporal amd later the _ lobes

cortical

pariteal

cloudy leptomeninges

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becuase there is loss of cortex in AD the ventricles enlarge and create a compensatory _ _ _

hydrocephalus ex vacuo

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2 pathologic hallmarks of AD

amyloid plaques and neurofibrillary tangles

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the # of _ correlated better with the degree of dementia in AD

neurofibrillary tangles

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plaques in AD are aggregates of _ peptides in the neuropil

(outside of the neuron)

Alpha B peptides

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tangles are aggregates of microtubulule binding protein _ they develop intracellularly and after neuroal death they persist

tau

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_ generation is the critical initiating event for the development of AD

AB plaques

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diseases in which Tau deposits appear and AB plaques do not AD _ (does or does not develop)

does not

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what encodes for TAU

MAPT

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the genetic locus on chromosome _ that encodes for _ has a strong influence on the risk of developing AD

Apolipoprotein E

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what is a neuritic plaque in AD

where are these located

also known as senile plques

neuritic processes around a amyloid core

HAN: hippocampus, amygdala and neocortex

amyloid core will stain with the congo red stain (derived from APP)

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what are the diffuse plaques in AD and where are the located

no amyloid core

CBS: cerebellar cortex, basal ganglia, superifical cortex

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down syndrome has an early onset of AD because

the gene encoding APP is on chromosome 21

presents the 2nd or third decade of life

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neurofibrillary tangles are bundles of _ in cytoplasm of neurons that displace the nucleus (not specific to AD)

they stain on

filaments

bielschowsky stain

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what is tau?

hyperphosphorylated axonal microtubule associated proteins that enhance microtubule assembly causing a tangle

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stain for TAU

MAP2 and ubiquitin

fundamental abnormaility in AD is deposition of _ peptides which are derived through processing of _ large burden of plaques and tangles is associated with severe cognitive dyfxn. tangles> plaques

AB peptide APP (amyloid precursor protein)

histology of AD (besides tangles and palques)

granulovacuolar degeneration hirano bodies

what are granulovacular degeneration

small clear intraneuronal cytoplasmic vacuoles (contain aygyrophilic granules) - apart of normal aging byt abundant in AD

what are hirano bodies major component

elongated glassy eosinophilic bodies with actin as its major compnent ## Footnote found in AD

_ _ _ invariably accompanied AD it has AB40 amyloid plaques and **thick vesseled walls **

cerebral amyloid angiopathy

frontotempoeral lobar degenerations are a group of disorders with focal degeneration of _ and _ lobes also known as frontotemporal dementia, share clinical findings like AD need to evalute post mortem to known the difference FTLD- Tau has _ only and the mutations may be in _ the . An example of this is _ TDP-43 has no _ and has 3 different genes (similar to ALS)

frontal and temporal tau , MAPT, pick disease and prgressive supranuclear palsy no tau

pick disease is a FTLD-Tau with lobar atrophy it is rare by has progressive _ early onset of _ changes with alterations in personality this is a _ sign and language distuburbances with is a _ sign

dementia behavioral changes ; frontal sign temportal sign

pick disease is atrophy of the frontal and temporal lobes with sparing of the _

posterior 2/3 of superior temporal gyrus

buzz words for pick disease

knife edge gyri (thin) pick cells (swollen) pick bodies (cytoplasmic innclusions, basophilic and stain with silver stain)

in picks disease only the _ lobes are affected not global like _

frontal AD

what is progressive supranuclear palsy

truncal rigidity and disequilirium difficulty wit heye movements nuchal dystonia, demenita, abnormal speech

progressive supranuclear palsy is a taupathy (PSP)- FTLD-TAU it is more common in _ (women/men) there is widespread _ loss there are _ neurofibirllary tangles with _ Tau straight filaments also considered a ?

men neuronal globose 4R atypical parkisonian syndrome/Parkinson Plus syndrome

vascular dementia is due to _ and imporves with treatment it is a progressive _ disorder associated with _ injury it affects the _ matter (white/gray/both) there will be areas of widespread _ clinical syndrome: _, _ abnormalities, _ signs, and focal neurologic defecits

vassculitis cognitive vascular injury both infarction (due to ischemia) dementia, gait abnormalities. pseudobulbar signs and nerologic defecits

what are psuedobulbar signs

frequent, involuntary and uncontrollable outbursts of crying or laughing that are exaggerated or not connected to your emotional state.

degenerative diseases of the basal ganglia and brainstem, are associated with _ disorders sympotms: (3)

movement rigidity, abnormal posturing, chorea

parkinsonism is damage to the _ _ system clinical sydrome of parkinsonism (4)

nitrostriatial dopaminergic system 1. diminished facial expression 2. slowness of movement (bradykinesia_ 3. fenestrating gait 4. rigidity and pill rolling tremor

wjat are the types of parkinsonisms

parkinsons disease Multiple system atrophy Post encephaltic parkeinsonism progressive supranuclear palsy

parkinsons disease is associated with protein accumulation, mitochondiral abnormalities, and neuronal loss in the _ _ hypokinetic movement is due to ? there is a progressive loss of _ response that is why we can treat with _. _ is adminsited in order to inhibit peripheral metabolism of _

substantia nigra loss of dopanergic neurons from the substantia nigra L-Dopa L-Dopa Carbidopa LEvadopa

what gene encodes for a synculein in PD (parkinsons disease) what chromosme is it on

SNCA chromosome 4a21

mitochondiral dysfunction in PD is caused b y mutations in ?

DJ-1, PINK1 and parkin

a synculein makes

lewy bodies

_ accounts for the juvinile autosomal recessive parkinsons disease

parkin

what is the most common gene causing of autosomal dominant PD

LRRK2

heterogenous mutations in _ are the most important risk factor for the development of PD

glucocerebrosides

in parkinsons there is pallor of the _ and _ there is loss of pigmented _ neurons associated with gliosis there are _ bodies that are located in the cytoplasm are eosinophilic. They are elongated and have a dense core surrounded by a pale _

substantia nigra and locus ceruleus catecholaminergic lewy halo (also a-synculein is present)

parkinsons disease CAN be accompanied by _ dysfunction

congitive

15% of PD patients develop _ and the incidence increases with age

dementia

there is a flutuating course of _ and prominent _ signs in dementia with lewy bodies

hallucinations frontal

dementia with lewy bodies has lewy bodies in _ locations and lewy _ that contain a syncuclein, there is depigmentation of the _ and _

cortical nitrites (dystrophic processes) substantia nigra and locus cerelus ## Footnote there is preservation in the cortex, hippocampus, and amygdala

the diagnosis is lewy body dementia when 1. dementia symptoms consitent with lewy body dementia develop _ 2. when both _ and _ symtpoms are present at the time of diagnosis 3. when dementia appears within _ _ after movement symptoms

first dementia and motor 1 year

the diagnosis of parkinsons disease dementia when a person is orginally diagnosed with parkinsons based on _ symptoms and dementia symptoms occur more than a year later

movement

atypical parkinsonian/ parkisonian plus syndromes

progressive supranuclear palsy corticobasal degeneration multisystem atrophy

what is the hallmark of atypical parkinsonian/ parkisonian plus syndromes

they all include parkinsonism as a component but they are minimmally responsive to L-dopa and they have additional signs and symptoms

corticobasal degernation is a progressive _ with extraprymidal _, asymmetric _ distuburbances (jerking of limbs) and imapired higher _ function (difficulty with skilled movement) _ decline will present later in disease tau lesions in the _

taupathy rigidity motor cortical cognitive decline later cerebral cortex

progressive subnuclear palsy has tau lesions in what regions?

brainstem and deep gray matter

CBD (corticobasal degeneration) Tau can be found in _ ( tufted) and _ (coiled bodies)

astrocytes oligodendrocytes

presence of _ positive threads in gray and white matter may be the most specific pathologic finding in corticobasal degernation

tau

in CBD the affected regions of the cortex shows _ neurons

ballooned

what is multiple system atrophy

an atypical sporadic syndrome that is sporadic and involves differeny systems in the brain

in multiple system atrophy there is _ cytoplasmic inclusions in _

alpha synclein oligodendrocytes

what are the three distinct neuroataomic systems involved in MSA

striatonigral circuit--> parkisonism olivopontencerebellar-> ataxia ANS--> autnomic dysfunction (orthostatic hypotension)

MSA has severe atrophy of the

basis pontis

huntingtons disease is autosomal _ it is a progressive _ disorder and _

dominant movement and dementia

huntingtons is degeneration of ?

striatal neurons

movement disorder in huntingtons

jerky. hyperkinetic involving all parts of the body (chorea)

HD repeat

polyglutamine trinucleotide on chromosome 4p16.3 CAG (10-35 copies)

average age of huntingtons disease

4-5th decade with an average of a 15 year death

COD of HD

penumonia and suicide

HD CAG repeates 40-50= _ onset >60= _ onset

adult juvenille

HD shows anticipation which are repeat expansions during _ leads to _ onset with _ transmission

spermatogenesis earlier parental

HD pathogenesis

loss of medium spiny striatal neurons leads to dysregulation of basal ganglia circuitry that increases motor output motor proceeds cognitive

med spiny striatal neurons normally _ motor activity

dampen

cognitice changes in HD is due to neurnal loss from the _

cortex

expansion in HD produces a toxic _ of function there are _ inclusions

gain intranuclear

in HD the brain is _ and there is striking atrophy of the _ _ and _ later globus pallidus is scondarily atrophied atrophy of _ lobes severity of symptoms is directly related to the degree of degeneration

small caudate nucleus putamen frontal ## Footnote caudate nucleus is decreased