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HP Theme 1 Neuropathology (Alzheimer)
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Theme 1: Neuropathology (Alzheimer’s disease)Aantekeningen colleges
Hippocampus bevind zich in het midden van de temporale kwab. Gyrus parahippocampalis worden
ook wel de reukhersenen (Entorhinal Cortex) genoemd. Daar krijg je de eerste afwijkingen.
Oorzaken dementie:
- Alzheimer (60%)
- Lewy body related dementie (10%) (Lewy bodies bevatten alfa-synucleine)
- Vasculaire dementie (10%)
- Parkinson dementie
- Frontotemporale dementie
Als er sprake is van atrofie, dan in deze volgorde : hippocampus temporale kwab frontale kwab
parietale kwab occipitale kwab
Amyloid β 42 stamt af van precursor protein APP. Als het verkeerd geknipt wordt (β + γ) krijg je Aβ
peptide. Dit eiwit vormt Aβ aggregaten en dit zorgt voor Amyloid fibrillen.
Tau is een transporteiwit en hyperfosforylatie leidt tot fibril formation.
Aβ is misschien mede verantwoordelijk voor de fosforylatie van tau.
Amyloid formatie voorkomen dmv :
- productie remmen door : γ en β secretase te remmen en α te stimuleren
maar γ-secretase speelt ook een rol bij Notch, dus je wilt die eigenlijk niet remmen (NSAID’s rem γ)
- aggregatie remmen door :tramiposate en scyllo-inositol
- increase degradatie + clearance door : immunotherapy, proteolyse, BBB transport
Familiair= 20 – 30 %
Sporadisch = 80 – 70 %
Late onset (>65 jaar) = 75 – 65 %
Early onset (<65 jaar) = 30 %
APP ligt op chromosoom 21.
c.1852G>C (Glu693Gln) is de mutatie die early onset Alzheimer veroorzaakt.
fenocopy : 1 andere vorm van dementie in de stamboom, alle andere hebben wel dezelfde vorm
APOE-ε4 is geassocieerd met late onset Alzheimer. Affects age of onset by shifting the onset curve
toward an earlier age.
Presenilinegenen PS1 en PS2 (betrokken bij γ secreate activiteit en NOTCH receptor proteins) zijn
geassocieerd met early onset Alzheimer.
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