Dietary cholesterol promotes repair of demyelinated lesions in the adult brain

[apod]

This is an interesting study I came across today:
http://www.nature.com/articles/ncomms14241

"Exogenous cholesterol enters the CNS through an impaired blood-brain barrier, resulting in enhanced repair and an amelioration of the neurological phenotype in two distinct models of remyelination. Our data suggest that cholesterol directly facilitates repair by modulating the profile of growth factor expression, promoting OPC differentiation and, together with the mitogen FGF2, potentiating OPC proliferation. Importantly, cholesterol supplementation does not exacerbate inflammation in EAE. The current study suggests that cholesterol provides a ‘fast track’ to remyelination and repair."

[Russ]

APOD, Interesting find. I take interest in the observation re statins that seems consistent with many discussions here:

"Further, cholesterol synthesis is enhanced during remyelination in mice29 and statin administration (inhibitors of sterol and isoprenoid synthesis) interferes with remyelination in the cuprizone model45. Nonetheless, monotherapy with statins ameliorates clinical scores in EAE; an effect associated with decreased CNS infiltration and inflammatory activity of T cells, likely reducing demyelination46,47,48. The outcomes of studies using statins in MS patients are contradictory, probably because of the disparate effects of statins on inflammation (beneficial46,47,48) and on remyelination (detrimental45). Accordingly, a recent meta-analysis does not recommend statin treatment for relapsing-remitting MS or clinically isolated syndrome49. Hence, we hypothesize that remyelination failure in MS reflects, at least partially, the inability to locally increase the cholesterol content in demyelinated lesions."

Russ

[Julie G]

This reminds me of a story that Dr. Bredesen often shares. Back in 2011, he and colleagues decided to search for "dementigens" by trialing every FDA approved drug (at the time) on an AD-mouse model to see which, if any, would lead to conversion to AD. Cerivastatin (Baycol) far away lead the pack. This is a lipophilic statin that crosses the BBB and has since been recalled by the FDA. You can read the resulting paper here. This quote from the abstract feels relevant for our community.

These results may have implications for the choice of which statins to evaluate in AD therapeutic trials; furthermore, the results may inform statin choice in individuals who are at high risk for the development of AD, such as those with an apolipoprotein E ε4 allele.

[Fiver]

This. Is what worries me. At least my statin is one less likely to pass the BBB.
But still....

[KatieS]

Tom, as a fellow statin user, I think there is a risk/benefit analysis. I would not opt for a statin if not for additional risk CV factors and will try to remain of the lowest dose. LG's doctor provided advise to use simvastatin for E4s. I'm on pravastatin, as the SV had a drug interaction for me. Of course, in mice (possibly marginally in the recent Medicare study) SV seems to have anti-inflammatory AD benefits. Do you have anyone in your family that seems to have benefitted cognitively from statin use?

[Fiver]

Hi Katie. Sorry I didn't see your note until now. I have CVD and dementia in the family. But interestingly, the CVD and dementia patients in our family are totally different. So I can't say if anyone has had cognitive benefits from statins.

Like you, I'm opting for a reduced dose. (The full dose gave me weird brain fog anyway - forgot things constantly!)

[circular]

Julie your link under 12 Feb above doesn't seem to go to Bredesen's paper about yhe dementagens. I'd love to see the other ones... And so helpful to know it's the lipophilic category of statins we should avoid when they're needed, or at least use as a starting point for choosing.

[circular]

Do pretty much all lipophilic molecules cross the BBB?

[Stavia]

Do pretty much all lipophilic molecules cross the BBB?

Great question Circ. Dunno....might depend on the size, and then also there is both active and passive transport across membranes ... so it's probably not that simple.

[circular]

Ah. Complications shmomplications, I want something to be simple. I suddenly remember the little grade school ditty about 'the shin bone's connected to the knee bone, the knee bone's connected to the ...lipophilic membrane barrier...' Maybe the meetup attendees will sing and demonstrate all this on video for us at the meetup party. Much easier to remember that way.