neurodegenerative and cognitive disorders

Question 1

what are the core neurodegenrative diseases?

Answer 1

Alzheimer’s,
Parkinson’s,
dementia with Lewy bodies,
motor neurone disease

Question 2

what is the cellular pathologies of core NDDs?

Answer 2

– a normal protein takes on an abnormal form

– misfolding, hyper-phosphorylation

– this aggregates into oligomers and later into visible inclusion bodies

– the protein’s normal function is lost; oligomers are toxic (inclusions too?)

– the neurone loses function, then dies, then disappears

Question 3

which proteins are involved in alzheimers?

Answer 3

tau- which normally stabilises microtubules

amyloid beta

Question 4

which protein aggregates in Parkinson’s?

Answer 4

alpha synuclein

Question 5

which proteins aggregate in motor neuron disease?

Answer 5

TDP-43 nuclear protein, binds DNA and RNA; aggregates in MND

Question 6

what are the different cognitive domains that can be affected in NDD?

Answer 6

• memory can’t learn, can’t remember, or learn then forget

–executive ‘remembering to do something’,organising, multi-tasking, efficiency

– language word-finding, wrong sounds in a word, short phrases, loss of word meaning

–visuospatial
gets lost, puts things in wrong places, can’t judge distance

–social-behavioural poor ‘manners’, doesn’t care, obsessive, apathetic, childlike

–psychiatric
low mood,anxiousoverminorthings,paranoid,visualhallucinations

Question 7

where does parkinson’s with levy bodies affect?

Answer 7

nigrostriatal neurones,

causing movement disorder

Question 8

where does dementia with levy bodies affect?

Answer 8

in cortical neurones,

causing cognitive disorder

Question 9

what methods are used to diagnose NDDs from one another?

Answer 9

– clinical syndrome (history, exam, cognitive tests)

– imaging (MRI, PET/SPECT, DAT scan)

– cerebrospinal fluid markers (Aβ, tau protein)

Question 10

which protein aggregates in frontotemporal lobar dementia?

Answer 10

• FUS

Question 11

describe alzheimer’s pathology

Answer 11

– neuronal inclusions: neurofibrillary tangles, containing tau protein

– beta-amyloid, containing Aβ protein – which are extracellular as a pose to intracellular as in other NDDs

– amyloid also often in walls of arterioles ‘cerebral amyloid angiopathy’

Amyloid appears first, tau location correlates with cognitive deficits
=> probably amyloid doesn’t damage neurones but triggers tau which does

Often co-exists with small-vessel cerebrovascular disease – this worsens cognitive deficits May also co-exist with Lewy body pathology

Question 12

what are genetic risk factors for alzheimer’s disease?

Answer 12

• genetic polymorphism:
  apolipoprotein E- epsilon 2,3, and 4, with 4 being the highest risk
• rare and dominantly inherited single genes include
  PSEN1 PSEN2 APP
• these cause early onset alzheimer’s in 30s and 40s

Question 13

explain the vascular risk factors on Alzheimer’s symptoms

Answer 13

Vascular risk factors: CVD worsens AlzD symptoms

Question 14

what are some genes associated with NDD?

Answer 14

C9ORF72,
GRN,
MAPT