Dementia Flashcards

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1
Q

Define dementia

A

A broad category of brain disease that causes long term and gradual decrease in memory, communication and ability to carry out daily activities

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2
Q

Risk factors of dementia?

A
Age
Genetic pre-disposition
Family history
Downs syndrome
Vascluar risk factor
Cognitive inactivity
Environment
Depression
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3
Q

What occurs in a patient with Alzheimers with their brain?

A

Extreme shrinkage of the hippocampus
Extreme shrinkage of the cerebral cortex
Severely enlarged ventricles

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4
Q

What genes for early onset?

A

APP
PSEN1
PSEN2

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5
Q

What genes for late onset?

A

APOE4

apolipoprotein

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6
Q

What is an amyloid precursor protein?

A

Transmembrane protein with a number of roles e.g. neural proliferation, migration, differentiation, plasticity and synaptogenesis

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7
Q

What are mutations in APP associated with?

A

Familial form of early-onset Alzheimer’s disease as well as cerebral amyloid angiopathy (CAA)

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8
Q

What do mutations in APP generally increase?

A

AB (beta) production

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9
Q

What decreases AB production?

A

A673T

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10
Q

What is the amyloid precursor protein (APP) cleaved by?

A

alpha-secretase
B-secretase
gamma-secretase

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11
Q

Which pathways is APP cleaved in?

A
Non-amyloidogenic pathway (alpha secretase and gamma secretase)
amyloidogenic pathway (B-secretase + gamma secretase)
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12
Q

What does the amyloidogenic pathway lead to the production of?

A

Ab 40-42

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13
Q

What are the subunits of gamma secretase?

A

Presenilin 1 (PSEN1) and presenilin-2 (PSEN2)

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14
Q

What enzyme is responsible for AB generation?

A

aspartyl protease

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15
Q

Which subunit of gamma secretase is more common in early-onset Alzheimer’s disease?

A

PSEN1

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16
Q

What is ApoE?

A

lipoprotein

17
Q

What is ApoE involved in?

A

cholesterol metabolism

18
Q

What alleles do ApoE have?

A

ApoE2
ApoE3
ApoE4

19
Q

What does ApoE4 show to decrease?

A

Decrease clearance of extracellular AB

20
Q

What is a Tau protein?

A

microtubule-associated protein

21
Q

What is the function of Tao?

A

Role in microtubule stabilisation and axonal transport

22
Q

how is tau-microtubule binding maintained?

A

Co-ordinated actions of kinases and phosphatases

Phosphorylation of Tau regulates its activity to bind to icrotubules

23
Q

What does hyperphosphorylation of Tau result in?

A

Formation of neurofibrillary tangles - primarily composed of paired felical filaments

24
Q

What does acetylcholine bind to?

A

Nicotinic

Muscarinic receptors

25
Q

What type of receptor are nicotinic?

A

Ion gated receptor channels

26
Q

What cations are nicotinic receptors selective for?

A

K+
Na+
Ca2+

27
Q

What type of receptor are muscarinic?

A

G protein receptors (GPCR)

28
Q

What is ACh synthesised from and by?

A

Choline and acetyl-coenzyme A (acetyl-CoA) by choline acetyltransferase (ChAT)

29
Q

What transfers ACh into synaptic vesicles

A

Vesicular acetylcholine transporter (VAChT)

30
Q

What promotes ACh exocytosis

A

Pre-synaptic neuron depolarisation

31
Q

What is Ach rapidly hydrolysed by?

A

Acetylcholinesterase (AChE)

32
Q

What acetate and choline recycled into?

A

High-affinity choline transporter (CHT1)