Given that tens of millions people have been treated for bipolar disorder with Lithium Carbonate, shouldn't researchers have already seen a correlation with Alzheimer's in patients?
Lithium carbonate was tested and didn't help the mice at all because it was just absorbed by the plaques. The exciting thing is they found a form of lithium (already commonly available as a supplement) which is not absorbed by the plaques and showed a reversal of symptoms with P=0.00007. That's the kind of statistical significance I like to see in my medical papers.
> Replacement therapy with lithium orotate, which is a Li salt with reduced amyloid binding, prevents pathological changes and memory loss in AD mouse models and ageing wild-type mice.
> LiOr is proposed to cross the blood–brain barrier and enter cells more readily than Li2CO3, which will theoretically allow for reduced dosage requirements and ameliorated toxicity concerns.
The important part is this: “a Li salt with reduced amyloid binding”
If cells in the brain are being deprived of lithium due to sequestration by amyloid beta plaques, then a bioavailable form of lithium that is resistant to sequestration may treat the pathology.
> We reasoned that the electrostatic interaction of the Li ion with Aβ deposits would be a function of the ionization capacity of the salt, and that Li salts with reduced ionization might show reduced amyloid sequestration. To assess ionization directly, we measured the conductivity of 16 lithium salts. Inorganic Li salts, including the clinical standard lithium carbonate (Li2CO3, hereafter LiC), showed significantly elevated conductivity, indicative of increased ionization, relative to organic Li salts (P = 8 × 10−4; Fig. 5a and Extended Data Fig. 7a). Of the organic Li salts, lithium orotate (C5H3LiN2O4, hereafter LiO) showed the lowest conductance across a broad Li concentration range (Fig. 5a and Extended Data Fig. 7a) and was therefore selected for further comparison with the clinical standard LiC.
From my not-exactly-expert understanding: lithium is a teeny tiny cation, and it can form compounds on a whole spectrum from ionic to covalent-ish. The authors are observing that lithium orotate does not fully dissociate in water.
