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Cell Path > Neurological Diseases 2 > Flashcards

Neurological Diseases 2 Flashcards

1
Q

What are 6 characteristic features of neurodegenerative disorders?

A
  1. Progressive loss of neurons
  2. Protein accumulation
  3. Age is the major risk factor
  4. They’re chronic diseases
  5. Sporadic or familial
  6. Can target specific regions of the brain
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2
Q

Problems with different proteins are associated with different neurodegenerative disorders. Which proteinopathies are associated with: Alzheimer’s disease, Parkinson’s disease, Motor Neuron Disease/Frontotemporal Dementia?

A

AD: TAUopathies
PD: SYNUCLEINopathies
MNR/FTD: TDP-43opathies

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3
Q

What are 5 brain characteristics of an ageing brain?

A
  1. Less efficient energy production
  2. Blood vessels changes - hypertension, atherosclerosis
  3. Atrophy
  4. Pigments + protein inclusions
  5. Cognitive decline
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4
Q

As the brain ages does the amount of grey or white matter or both change?

A

No change in grey matter. White matter decreases at a rate of 2mL/year.

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5
Q

When is AD most likely to occur? Is it easy to diagnose?

A

In the 8th decade. No, there aren’t any definitive tests except for looking at the brain during autopsy.

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6
Q

What is 1 MACRO and 4 MICRO features of AD?

A 
Macro: 
1. Atrophy
Micro:
1. Beta amyloid plaques
2. Tau neurofibrillary tangles
3. Gliosis
4. Loss of neurons
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7
Q

Atrophy of brain with AD:

Early on: End stage:
_______ atrophy –> ___ + ___ atrophy –> ____ atrophy

A

Hippocampal

Hippocampal and temporal

Global

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8
Q

What are 3 features of beta-amyloid plaques?

A
  1. Variable in terms of size and shape
  2. Found throughout neocortex
  3. Mainly comprise beta-amyloid
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9
Q

What are 5 features of neurofibrillary tangles?

A
  1. Bundles of neurofilaments in the cytoplasm of neurons
  2. Found mainly near: hippocampus, temporal lobe
  3. Made up of paired helical filaments (PHF)
  4. Made up mostly of hyperphosphorylated tau
  5. The spread of the tangles is correlated with the severity and progression of the disease
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10
Q

The tangles and plaques don’t really overlap but when they do they are known as _______.

A

‘Neuritic’ plaques

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11
Q

In non-amyloidogenic proteolysis, Amyloid Precursor Protein (APP) is cleaved by ________?
In amyloidogenic proteolysis, Amyloid Precursor Protein (APP) is cleaved by ________?

A

Alpha and gamma-secratase

Beta and gamma secratase

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12
Q

What are the 4 stages on NFT progression?

A
  1. Pre-tangle
  2. Early
  3. Mature
  4. Ghost
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13
Q

What % of all AD cases are familial?

Familial AD is the result of (known) mutation in 1 of 3 proteins. What are they?

A

<2%

  1. Amyloid Precursor Protein (APP) (rarest)
  2. Presenilin 1 (commonest)
  3. Presenilin 2

*** Mutations in tau have not been found in familial AD

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14
Q

What are the 6 steps in the Amyloid Cascade Hypothesis proposed for development of sporadic AD?

A
  1. Dysregulation of APP metabolism
  2. Production of soluble oligomeric forms of beta amyloid
  3. Altered neuronal ionic homeostasis
  4. Altered kinase/phosphatase activities
  5. NFT formation
  6. Neuronal dysfunction + death
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15
Q

What are the 5 known risk factors for development of sporadic AD?

A
  1. AGE!!!
  2. Female
  3. Dementia in first degree relative
  4. Inheriting the e4 allele of the Apolipoprotein E (ApoE) gene
  5. Multiple small effects of other gene variants
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16
Q

______ > protective = sAD

A

risk factors

17
Q

There are 3 variations of the ApoE gene - e2, e3 and e4. Why is inheritance e4 not good compared to inheriting the other two.
Inheriting 1 x e4 allele increases the risk of AD by ___.
Inheriting 2 x e4 allele increases the risk of AD by ___.

A

ApoE thought to have a role in breaking down beta amyloid plaques. 2 + 3 are good at this but 4 is shit, meaning plaques build up.
Doubles it –> 2x
12x !!!!

18
Q

Can we use beta amyloid modifying therapies to prevent cognitive decline.

A

No - people who are against the Amyloid Cascade Hypothesis show that it doesn’t halt cognitive decline. It would need to be introduced v early on. These people also think beta amyloid is not primarily respponsible as well for AD. Instead maybe: tau? oxidative stress? inflammation?

19
Q

What does DIAN stand for and what is it? Who is recruited?

A

Dominantly Inherited Alzheimer Network.
A study that aims to find biomarkers for Alzheimer’s disease that are detectable long before the initial clinical symptoms.
People with siblings or parents who have AD.

20
Q

Area of research for a potential AD cure?

A

Stem cells - however it is expensive, ethics, invasive.

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