Here's a brand new open access paper from Dr. Bredesen describing the three unique Alzheimer's disease subtypes that have emerged from his dataset. This information was previously shared with those of us who met with him in May.
The cause of Alzheimer's disease is incompletely defined, and no truly effective therapy exists. However, multiple studies have implicated metabolic abnormalities such as insulin resistance, hormonal deficiencies, and hyperhomocysteinemia. Optimizing metabolic parameters in a comprehensive way has yielded cognitive improvement, both in symptomatic and asymptomatic individuals. Therefore, expanding the standard laboratory evaluation in patients with dementia may be revealing. Here I report that metabolic profiling reveals three Alzheimer's disease subtypes. The first is inflammatory, in which markers such as hs-CRP and globulin:albumin ratio are increased. The second type is non-inflammatory, in which these markers are not increased, but other metabolic abnormalities are present. The third type is a very distinctive clinical entity that affects relatively young individuals, extends beyond the typical Alzheimer's disease initial distribution to affect the cortex widely, is characterized by early non-amnestic features such as dyscalculia and aphasia, is often misdiagnosed or labeled atypical Alzheimer's disease, typically affects ApoE4-negative individuals, and is associated with striking zinc deficiency. Given the involvement of zinc in multiple Alzheimer's-related metabolic processes, such as insulin resistance, chronic inflammation, ADAM10 proteolytic activity, and hormonal signaling, this syndrome of Alzheimer's-plus with low zinc (APLZ) warrants further metabolic, genetic, and epigenetic characterization.
Yes, thanks to the good doctor, this is scary reading at times but good and necessary. And generous of him.
In light of this, can anyone recall why a sign is posted somewhere in my mind telling me to Fear Zinc? I was already trying to get back to that issue and this is another reason.
I'll share what I've learned from Dr. Bredesen about this Cortical subtype. It seems to be the result of a toxic or infectious exposure. High copper/low zinc appears to be the tip-off that that may be the case. So far, E4 seems to provide some protection perhaps via amyloid beta production. Dr. Bredesen falls into the camp that views it as protective- a part of our pro-inflammatory arsenal.
As far as fearing zinc??? From what I've gleaned (and Dr. Ram has directly shared,) Dr. Bredesen is in favor of optimizing levels.
What do the numbers look for people of the same age with various non-dementia health complaints? how many of them would feature low zinc levels and the other abnormalities listed in the article?
That's the question, I think. What constitutes optimal, and if copper is high due to diet (lots of nuts) is supplementing zinc to get the ratio right? Or just accept it and not tinker? "Supplementing metals" seems to have been something that someone somewhere said not to do. I'm not really acting on that -- I'm supplementing zinc very conservatively to nudge the ratio in the right direction, mainly because I didn't like any of the canned smoked oysters I found and more convenient than stopping by the fish store to pick up a few fresh ones once a week. Cheaper, too.
marthaNH wrote:That's the question, I think. What constitutes optimal, and if copper is high due to diet (lots of nuts) is supplementing zinc to get the ratio right? Or just accept it and not tinker?
Agree completely that this is the question, and also agree with your reasoning and intuition about it. My soft conclusion (all my conclusions are soft these days, actually) is that plant-heavy diets, esp. if they contain a lot of nuts and seeds, 1) are very healthy, and 2) will have a very high Cu:Zn ratio (by RDAs, mine is 4:1 or so; higher on cashew-heavy days). "Nudge" is exactly the word I use when thinking about Zn supplementation. Plant-heavy diets are good for health (including brain health). Would they be even better if the Cu were removed? Maybe. Or maybe they'd be worse. We don't know. Still, all this talk of Cu:Zn ratios!!! OK, I'll just nudge the ratio with a bit of Zn, I (softly) conclude. But even that might be a mistake. I think evolution knows more than I do.
Gilgamesh wrote:Still, all this talk of Cu:Zn ratios!!! OK, I'll just nudge the ratio with a bit of Zn, I (softly) conclude. But even that might be a mistake. I think evolution knows more than I do.
When nudging your ratio, are you looking at a daily ratio with small amounts of zinc, or a weekly ratio with a larger bump? My Zn:C ratio is often around 5-6 without supplementing, where a couple 30mg L-optizinc capsules budges my weekly avg. over 8.
My inclination is to err on the low side with supplements but eat all the oysters. So I do daily very small doses of zinc. That's based on nothing but fear of "bolus". I think that's the word.
