Midterm Two

Question 1

what are the 3 categories of brain disorders

Answer 1

neurodegenerative, psychiatric, neurodevelopmental

Question 2

what are some examples of neurodegenerative diseases?

Answer 2

alzheimer’s, huntington’s, parkinson’s, ALS

Question 3

Alzheimer’s is primarily _______. but some rare _______ forms have early onset (before age 65)

Answer 3

sporadic, familial

Question 4

define Alzheimer’s

Answer 4

progressive loss of brain function due to increasing synaptic connections, degeneration of axons and dendrites, and eventual death of neurons

Question 5

what are the two defining AD pathological lesions

Answer 5

amyloid plaques, neurofibrillary tangles

Question 6

beta amyloid (A-Beta) has a strong tendency to fold into

Answer 6

Beta pleated sheets

Question 7

amyloid plaques drive from

Answer 7

amyloid precursor protein

Question 8

A-beta forms from what process

Answer 8

proteolytic processing

Question 9

sequential cutting by what creates A-beta monomers? After, what do the monomers readily aggregate into?

Answer 9

B-secretase and gamma-secretase. oligomers

Question 10

why does normal A-beta production not cause pathology

Answer 10

because it is continually cleared into the CSF and then the blood

Question 11

when does a-beta become toxic

Answer 11

when it accumulates in the brain

Question 12

early AD can occur in _______ syndrome

Answer 12

down

Question 13

____ gene affects risk of developing AD

Answer 13

APoE

Question 14

the APOE gene belongs to a family of lipid-binding proteins called

Answer 14

apoliproteins

Question 15

individuals with APOE_ and APOE_ confer the HIGHEST risk of AD

Answer 15

4/4

Question 16

the age of onset of AD is ________ on average with the APoE4 allele

Answer 16

earlier

Question 17

extracellular plaques = excessive _______
intracellular tangles = abnormal ______

Answer 17

Abeta, tau

Question 18

what is the abeta hypothesis

Answer 18

overproduction of Abeta is the direct and primary cause of AD

Question 19

what is the tau hypothesis of AD

Answer 19

abnormal phosphorylation and missorting of tau is direct and primary cause of AD

Question 20

microtubules exhibit ______ ______ in cells. alternating periods of growth and shrinkage

Answer 20

dynamic instability

Question 21

tau is a __________-associated protein

Answer 21

microtubule. binds along microtubules to stabilize them and regulate cargo transport

Question 22

tau binding to microtubules is regulated by

Answer 22

phosphorylation

Question 23

in AD, tau becomes missorted to

Answer 23

dendrites

Question 24

the number of neurofibrillary tangles is a better indicator of

Answer 24

AD severity

Question 25

_________ is a class of neurological disease characterized by presence of tau-containing NFT

Answer 25

taupathies

Question 26

braak stages in AD

Answer 26

progressive spread of P-tau-containing NFTs beginning in entorhinal cortex, eventually spreads to many cortical regions throughout brain

Question 27

sporadic genetic causes of AD

Answer 27

PS1, PS2, APP

Question 28

familial genetic cause of AD

Answer 28

APOE

Question 29

what are the three main pathological signs in the brain indicating presence of AD

Answer 29

1. abeta plaques 2. tau tangles 3. reactive microglia

Question 30

_________ also plays a critical role in AD

Answer 30

neuroinflammation

Question 31

hallmarks of PD

Answer 31

loss of motor fxn - tremor - rigidity - slowness, difficulty initiating movement - posture and gait instability

Question 32

PD affects what part of brain

Answer 32

midbrain

Question 33

DA neurons in the _______ _________ in the midbrain die in PD. this leads to less DA release in the __________

Answer 33

substantia nigra, striatum

Question 34

precursor of DA

Answer 34

L-DOPA

Question 35

DA neurons in SN project to

Answer 35

striatum

Question 36

DA neurons in VTA project to

Answer 36

cortex, forebrain

Question 37

catacholamines are derived from

Answer 37

tyrosine

Question 38

what creates L-DOPA

Answer 38

tyrosine hydroxylase

Question 39

__________ is a drug often given to patients with PD

Answer 39

L-DOPA. replaces dopamine

Question 40

what is the problem of using L-DOPA as a drug

Answer 40

eventually all neurons that make DA die

Question 41

___ ____ are a characteristic pathology in PD

Answer 41

lewy bodies

Question 42

lewy bodies contain

Answer 42

misfolded aggregated fibrils of alpha-synuclein

Question 43

HD is hereditary. it is _____ __________

Answer 43

autosomal dominant

Question 44

HD occurs from degeneration of _______ neurons in the __________

Answer 44

GABAergic, striatum

Question 45

genetic basis of HD

Answer 45

expansion of CAG nucleotide repeats

Question 46

CAG encodes glutamine (Q) therefore, HD is a __________ disorder

Answer 46

PolyQ

Question 47

______ is a chronic neurodegenerative disease that affects motor neurons

Answer 47

ALS

Question 48

ALS attacks both ____ and _______ motor neurons

Answer 48

upper and lower

Question 49

most ALS cases are __________

Answer 49

sporadic

Question 50

in ALS, RNA binding protein ______ loses its normal fxn in gene regulation and forms aggregates

Answer 50

TDP-43

Question 51

limb vs bulbar onset ALS

Answer 51

limb: begins in arms or legs bulbar: sx in speech or swallowing problems

Question 52

order of mutated genes in ALS by prevalence

Answer 52

C9orf72, SOD1, TARDBP, FUS

Question 53

nearly ALL patients have clumps of _____ in their motor neurons even without _______ mutations

Answer 53

TDP-43, TARDBP

Question 54

hemorrhagic stroke

Answer 54

burst vessels

Question 55

ischemic stroke

Answer 55

blocked vessel

Question 56

early on in a stroke, neurons die via _______ __________ (pathological cell swelling) or a form of necrotic cell death

Answer 56

cytotoxic edema

Question 57

at later times in a stroke, neurons die via _____

Answer 57

apoptosis

Question 58

core of stroke

Answer 58

area of intial damage due to low blood flow. death via cell edema. irreversible

Question 59

penumbra

Answer 59

area of cell stress and partial damage, may be rescuable if treated early. death via apoptosis

Question 60

what is ionic cause of cytotoxic edema

Answer 60

excess sodium and chloride entry, causing osmotic stress

Question 61

"Spreading depolarization" driven by _______ recruits more neurons to be damaged in a stroke

Answer 61

glutamate

Question 62

excess intracellular calcium damages ________

Answer 62

mitochondria

Question 63

penetrating TBI

Answer 63

skull fracture, gunshot

Question 64

diffuse TBI

Answer 64

blunt head trauma (sports, falls, warzone)

Question 65

concussions are considered a ____ TBI

Answer 65

mild

Question 66

repeated mild TBI causes

Answer 66

chronic traumatic encephalopathy (CTE)

Question 67

CTE is a

Answer 67

taupathy

Question 68

CTE tau tangles begin in depths of

Answer 68

sulci