The BBB Delusion

Or why the blood brain barrier is not a barrier to aluminium

I am aware that many of you avidly spreading the gospel according to Mr Aluminium have often had your arguments countered by aluminium bigots telling you that aluminium cannot cross the blood brain barrier (BBB). Of course, you can begin the defence of your position by asking how it is then possible that multiple research groups across the globe, and notably my own, have consistently measured aluminium in brain tissue. How did it get there if aluminium cannot cross the BBB. I suppose that industry stooges such as they are will simply dismiss all such data as contamination. As we know to our cost from the era of covid it is all too easy to dismiss science that doesn’t fit the narrative.

As a Professor of Biology at Keele University I lectured neuroscience students on myriad subjects including the blood brain barrier. I have to say that I too learned a great deal from preparing and giving lectures and one thing that struck me regarding the BBB is how easily this barrier is compromised by all manner of substances. I used this new found knowledge to think about how aluminium gained entry to the brain and I produced the figure below to help me.

The figure is taken from a paper I wrote on Aluminium in the Human Brain. The BBB is a specialised endothelium (cell layer). Like all epi-/endothelia adjacent cells are held together by a calcium-based cement and, in some instances, structures called tight junctions. These connections between cells are especially impermeable and the BBB has more such types of junction than other membranes. However, these tight junctions are only one of the properties of the BBB that confer its (clearly legendary) reputation as an impermeable barrier. The BBB is a highly selective membrane which means that it has a high density of transport routes (active and passive) both to allow entry of substances into the brain, such as glucose, but also to help remove substances from the brain. The latter is one very good reason why drugs targeting brain tissue need to be administered at very high doses to help to counter the rate at which they are expelled from the brain. Essentially most such drugs are ineffective not because they cannot gain entry to the brain but because they are removed from the brain before they can act at their chosen target. Those of you interested might like to look up the story of L-dopa used in the treatment of Parkinson’s disease as an example of this. I am digressing. Perhaps one of the most surprising properties of the BBB, one that certainly surprised me and entertained the students, is something called ‘residual leakiness’. Yes, you read that correctly, the BBB always allows about 10% of blood-borne components across its surface and into brain tissue. So, the point I am trying to put across is that it is not so difficult for something, such as aluminium, to cross the BBB but it may be more difficult for that substance to remain in brain tissue. The rules governing the permeability of the BBB have been honed over time immemorial through natural selection. Aluminium, as I have explained in previous substacks and in detail in my book, has not played a part in this selection. So, how does aluminium cross membranes such as those that constitute the BBB.

I wrote about this in what has become a seminal paper on this subject. The figure shown below is taken from this paper.

Fig. 1. (A–F) The transport of aluminium across biological membranes. (A) There are 5 major routes by which aluminium could be transported across cell membranes or cell epi-/endothelia; (1) paracellular; (2) transcellular; (3) active transport; (4) channels; (5) adsorptive or receptor-mediated endocytosis. There are 5 major classes of forms of aluminium which could participate in these transport routes. (i) Free solvated trivalent cation (Al3+(aq)); (ii) low molecular weight, neutral, soluble complexes (LMW-Al0(aq)); (iii) high molecular weight, neutral, soluble complexes (HMW-Al0(aq)); (iv) low molecular weight, charged, soluble complexes (LMW-Al(L)x+/− n (aq); (v) nano and micro-particulates (Al(L)n(s)).

Again, those of you interested in the detailed science behind the movement of aluminium across biological membranes should read the paper. When I wrote this paper I had not yet had the epiphany brought to me by the microscopy of my colleague Dr Matthew Mold. When I wrote the paper I was frankly unaware that immune-reactive cells from the periphery could enter the brain by simply squeezing between cells in the BBB. When the brain is under attack, for example from a microbe, and suffers some form of inflammation, the brain signals to the body for help and immune-reactive cells in the periphery such as macrophages respond to the signal by crossing the BBB to attend the problem. What happens if these immune-reactive cells are already loaded with aluminium, perhaps obtained from a vaccine injection site, and carry their toxic cargo of aluminium into the brain. This is what we observed in our research on aluminium in brain tissue in autism and this added a completely new perspective on how aluminium enters brain tissue.

The blood brain barrier is a beautiful product of biochemical evolution and natural selection and acts to maintain the only immortal cell line in our body, the neurones. However, its success is not in its lack of permeability but in its ability as a selective barrier. Unfortunately this unique property evolved in the absence of biologically available aluminium and it is now too a target of the toxicity of aluminium. Tell this to the BBB bigot.