New paper led by @silvia-anderle.bsky.social Lifestyle matters for genetic Alzheimer’s disease risk: APOE4 reduces neurovascular function most in an already-stressed system, when neurons are active and mice do less exercise. I'll tell you all about it! 🧪 #neuroscience #alzheimers rdcu.be/d74uh - ThreadSky

cathnaledi.bsky.social • 107 days ago

New paper led by @silvia-anderle.bsky.social

Lifestyle matters for genetic Alzheimer’s disease risk: APOE4 reduces neurovascular function most in an already-stressed system, when neurons are active and mice do less exercise.

I'll tell you all about it! 🧪 #neuroscience #alzheimers

https://rdcu.be/d74uh

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leonsmyth.bsky.social•107 days ago

Congrats Catherine!! 🤩

cathnaledi.bsky.social•107 days ago

Thanks Leon!

cathnaledi.bsky.social•107 days ago

APOE4 increases your risk of getting Alzheimer's disease (AD), which is linked to early blood flow changes in the brain. So does APOE4 impair brain blood flow? Previously Orla Bonnar and @kirasha.bsky.social found APOE4 has only subtle effects on vessel function https://journals.sagepub.com/doi/full/10.1177/0271678X231172842

cathnaledi.bsky.social•107 days ago

But others studying anaesthetised mice found big effects of APOE4 on blood vessels. Why the difference? Well, Orla's mice were super-fit and healthy with an exercise wheel in their cage. Exercise protects from dementia - were Orla's mice' blood vessels protected?

cathnaledi.bsky.social•107 days ago

Silvia tested this by comparing neurovascular function in APOE4 (increased AD risk) and APOE3 (normal AD risk) mice but in some mice she took their exercise wheel away!! These mice were indeed less active.

cathnaledi.bsky.social•107 days ago

She measured *loads* of different aspects of neuronal and vascular function (e.g. calcium signals in neurons, blood flow, blood oxygen, how well different vessels dilate) Generally more active mice had better neurovascular function, and less active mice had worse.

cathnaledi.bsky.social•107 days ago

But mice with the genetic risk factor for AD - APOE4 - were especially sensitive to exercise. The worst neurovascular function was consistently seen in APOE4 sedentary mice.

cathnaledi.bsky.social•107 days ago

And the reduction in neurovascular function in these APOE4 sedentary mice was biggest when neurons were active - when they are using more energy so need more blood flow. So there's a bigger effect when the system is under pressure.

craigedbrown.bsky.social•107 days ago

Very impressive work @silvia-anderle.bsky.social . Figure 7 is brilliant.

silvia-anderle.bsky.social•107 days ago

Thank you Craig 🙌🏼

cathnaledi.bsky.social•107 days ago

Thanks so much Craig!!

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