Is the Definition of Alzheimer’s Being Changed to Sell Drugs?

Biological Blood Markers – Bio-Markers

There is, however, growing pressure to re-diagnose Alzheimer’s based on the presence of biological blood markers called bio-markers.

The two bio-markers being focussed on relate to:

– Amyloid, a toxic peptide (a bit smaller than a proteinProteins are large molecules consisting of chains of amino acids. Proteins are essential nutrients for the human body – they are a building block of…) and
– Another messed up protein found in the brains of those with dementia, called p-tau.

Amyloid plaques are found in the brains of some, but not all with Alzheimer’s. Not all with high amyloid burden in the brain, develop dementia. So it is not a ‘proof’ of pending dementia. Also, despite numerous trials costing billions of dollars, no treatment that lowers amyloid burden by injecting antibodies that seek and destroy amyloid have yet produced a clinically significant benefit. For these reasons high amyloid cannot be classified as ‘causal’ although some pretend it is. The weight of scientific evidence has reasonably established that it is not causal.

On the other hand P-tau accumulation is almost always seen in the demented brain and leads to tangles of nerves called ‘neurofibrillary tangles’. Since there are no drugs that successfully lower p-tau with cognitive benefits there is therefore yet to be a good enough case for causality but the association is certainly strong. Tau, gets messed up and becomes ‘phosphorylated’, (abbreviated to ‘p-tau’) when a person lacks B vitamins and has raised homocysteineHomocysteine is an amino acid found in the blood. Elevated levels of homocysteine have been associated with narrowing and hardening of the arteries, an increased….[1] So accumulation of p-tau may be, at least in part, a consequence of raised homocysteine (above 11 mmol/l), which has been established as causal, as in modifying the disease process, because, when lowered with B vitamins, the rate of cognitive decline and brain shrinkage slow down considerably and, in some, even get arrested.

Despite the unparalleled evidence for homocysteine as potentially causal and an essential biomarker it is largely being ignored as witnessed by its exclusion from the recent Lancet Commission on dementia prevention, and the refusal to publish a critique written by members of our Scientific Advisory Board, which is now published in the leading Journal of Alzheimer’s Disease.[2] This is well worth reading by all to see how competitive avenues are effectively closed down. Homocysteine, in both the US and UK, is a simple test that doctors can’t access because it isn’t on the approved lists of tests for dementia. Yet, testing and correcting it would, according to Oxford University’s health economist, save over £60 million a year.[3]

There is, however, a massive push to redefine Alzheimer’s just on the basis of high amyloid and p’tau. Why?

Redefining Dementia

Some would say that having a simple blood test to say if a person is heading for dementia is a great benefit since those MRI brain scans used to diagnose Alzheimer’s are expensive. (Cognitive Function Tests aren’t – ours is free.) Also, the more ‘markers’ we have for risk the sooner one could act to prevent dementia developing. That, for example, is why we recommend everyone with any cognitive decline have their homocysteine level tested.

The cynical would say that redefining dementia, or risk for dementia, based on amyloid and p-tau does two potentially profitable things: firstly, if you do have patentable and profitable treatments that lower amyloid and p-tau it helps sell them; and secondly, it expands the market beyond those with dementia or pre-dementia, as defined by a Cognitive Function Test, so you can sell more of these drug treatments. They’d also question why there is a need to even have a blood test if dementia is cognitive decline and cognitive function is easy to test and picks up those at risk several decades before a diagnosis? I mean would you have a blood test to determine how fit you are? We’ve run 470,000 tests and it is very clearly that cognitive function steadily declines over age and therefore one can pick up those at risk simply from a cognitive function test. If the only goal were to find those at risk there is no specific need for a blood test. But if the goal were to then recommend a ‘treatment’ you’d need to go one step further.

Food for the Brain recommend testing things that are known to drive risk, and lower it, if changed. Homocysteine, omega-3 index, vitamin DWhat it does: Helps maintain strong and healthy bones by retaining calcium. Deficiency Signs: Joint pain or stiffness, backache, tooth decay, muscle cramps, hair loss…., glutathione for antioxidants and HbA1c for blood sugar. Having a poor result in these tests helps a person know what to do such as taking homocysteine-lowering B vitamins, omega-3, vitamin D, antioxidants, less sugar and carbs. We also include a diet and lifestyle assessment with our Cognitive Function Test so we can guide people as to which diet, lifestyle changes would be expected to reduce their risk.

The danger of the ‘two step dance’ where the ‘blood test’ becomes the disease, is akin to what happened with heart disease. Everyone in the medical pipeline was cajoled into thinking high cholesterol equals risk for heart disease. Tons of research money poured into this narrative with now 90,000 studies on cholesterol.  I never bought into this because the basic logic – eat eggs high in cholesterol, get cholesterol stuck in your arteries and die of a heart attack – didn’t add up. The latest study actually showed that eating two eggs a day, provided you don’t have a high intake of saturated fatSaturated fats should be avoided wherever possible as they increase the amount of cholesterol in the blood and increase the risk of developing heart disease…., lowers blood cholesterol[4], and other studies show that eating eggs decreases risk for both heart disease and dementia[5]. Even if high cholesterol did increase risk for heart disease one has to ask ‘what causes high cholesterol?’ For example, eating lots of sugar and carbs and a basic bad, western, refined food, sugar-laden diet, raise cholesterol. In other words, high cholesterol could be and almost certainly is a consequence, not a cause of heart disease. The same questioning needs to be applied to amyloid and p-tau.

The proof of causality requires a treatment that lowers the marker, for example cholesterol, and lowers the disease risk, in this example for heart disease. Statins drugs, which made more than a trillion dollars in sales, do lower cholesterol, but, extraordinarily, according to Dr Malcom Kendrick, cholesterol expert and author of the book ‘The Clot Thickens: The Enduring Mystery of Heart Disease’ no independent study not run by the statin makers, has shown benefit for those with heart disease, let alone those without. In his book and my podcast with him, you’d learn that, not surprisingly, many of the same contributors to dementia – raised homocysteine, lack of antioxidants, too much sugar, lack of omega-3, stress, lack of exercise, all play a role in developing heart disease. But so all pervasive and persuasive has been the push to establish ‘cholesterol=heart disease’ that you’d be in the majority if you thought this surely must be true and even ridiculed if you questioned statins.

Dr Malcolm Kendrick was attacked in the Daily Mail as a ‘statin denier’, sued them and won. It costs the Mail several million pounds because they, not he, had misrepresented the scientific facts and denigrated his reputation in the process. After all, doctors are even recommended a calculator by the National Institute of Health and Care Excellence (NICE) into which you put a person’s age and their cholesterol level and it says ‘prescribe statins’. Those in the know watched a process known as ‘diagnostic creep’ whereby the acceptable level of cholesterol, which was over 6mmol/l  until statins came into existence, then got lowered to 5mmol/l on the basis of ‘consensus’ of a group of cholesterol experts most of whom were directly or indirectly in the pay of the statin makers. This lowering of the cholesterol level vastly expanded the potential criteria for prescribing statins, thus massively increasing the market. GPs are even financial rewarded for testing cholesterol and lowering it under the QOF scheme, rescinded in Scotland several years ago but still running in England.

A similar thing may now be happening in relation to dementia and Alzheimer’s. There’s already over 60,000 studies on amyloid and tau, which is a lot of research money spent, and literally hundreds of billions of dollars invested in this narrative. The likely blood test equivalent of cholesterol is the ratio of a type of amyloid called amyloid42 that is lower in the bloodstream when it is high in the brain, and a type of p’tau called p’tau217 which correlates pretty well with a high level in the brain. If you AI search on this it says ‘Amyloid 42 (Aβ42) and phosphorylated tau 217 (p-tau217) are crucial blood-based biomarkers for diagnosing Alzheimer’s Disease (AD)’ The reality is that it is not crucial for diagnosing Alzheimer’s. Alzheimer’s has and should be diagnosed on the basis of a scan of the medial temporal lobe for decades.

Also, the first licensed biological test for dementia, called Lumipulse, is based on just this ratio, despite the study being rather circumspect.[6]How was this license achieved? Two establish that a blood test reliable predicts a disease, in this case Alzheimer’s, hat you should do is have two groups, one with diagnosed Alzheimer’s and one without (properly diagnosed on the basis of a Cognitive Function Test and a brain scan) then see how well the the ratio of amyloid 42/p’tau 217 predicts who is in which group. In this study they first changed the diagnosis of Alzheimer’s on the basis of ‘consensus’ to mean those with high amyloid and p’tau in their brains from looking at the cerebrospinal fluid (CSF) levels from a lumbar puncture. Then they eliminated any ‘intermediary results’. Then they showed that those with very high amyloid and p’tau in their brains had a poor amyloid/p’tau ratio in their blood. This is hardly surprising and doesn’t really teach us anything. But that was enough to get a licence.

The amyloid/p’tau pitch was the leading story in the Journal of the American Medical Association’s editorial last month[7]  talking about this and that kind of amyloid and p’tau, in this and that part of the brain, and studies with various models trying to make the cap fit.

Also, there are conferences all over the world, ultimately and primarily funded by pharma, with complicated science presented by so-called experts to hoodwink everyone into the validity of targeting amyloid and p’tau much like the story of the Emperor’s New Clothes. Yet even if this were a valid biomarker for risk there are still no clinically effective drug treatments. Those anti-amyloid antibodyAn antibody is a protein produced by the body’s immune system when it detects a harmful substance known as an antigen. Examples of antigens include… injection drugs that did get licensed in the UK and US, but nor the EU, showed such tiny benefit against massive costs, not least because a quarter got brain bleeding and swelling, thus requiring brain scans with each injection, thus cranking up the actual cost of treatment. Also, something close to one in 200 died. NICE, who advised UK GPs and the NHS what to prescribe, ruled that they were not cost-effective. In the US the Food and Drug Administration’s ten experts voted not to licence one of these drugs. Nine said ‘no’, one abstained but the FDA went ahead with the licence. Many experts resigned in protest as political and financial pressure overruled the science. This is hardly surprising since the pharma watchdog, the FDA, and thew equivalent body in the UK, the MHRA, are largely funded by the pharmaceutical industry that it polices.[8]

There are two glaring ironies here: the first in that the main argument for blood tests to be used to diagnose dementia or Alzheimer’s and those potentially at risk is that MRI brain scans are expensive, yet the reality of a very high adverse effect rate from the drug treatments means that MRI brain scans have to be run anyway with each injection to check the brain isn’t bleeding or swelling.

The second is the discovery that amyloid is actually produced to stop brain bleeds according to research by Australian Professor Jonathan Stone[9]. In my podcast with him he points out that no demented brain shows less than a thousand points of damage caused by micro-bleeds (a stroke is a big bleed). So, amyloid is the fireman, not the fire as you’d expect. On that basis, then removing it would cause bleeding in many, which is exactly what is happening. By the way, all dementia is vascular, with clear evidence of damaged blood vessels in the brain, but ‘vascular’ dementia is diagnosed when there a major bleed, a stroke, and then a big drop in cognitive function.

What Next?

What is even more concerning is that if this line of marketing is successful even younger people, without evidence of brain shrinkage, could be tested for this amyloid/p’tau ratio and deemed ‘at risk’. Then they would potentially be offered a drug treatment that causes bleeding in a significant minority, thus causing a ‘fire’ which would trigger amyloid deposition to stop the bleed. Many top scientists have been questioning for years[10] the ethics of doing any more trials of these anti-amyloid treatments, let alone on younger people without dementia. But the push to establish the two-step dance based on amyloid and p’tau, continues. Even the word ‘prevention’ is being hijacked to mean early drugs.

We, the public, and even your GP, would not be sufficiently trained in the details of science to know what that blood test ratio should be. Instead, there would be an army of eminent experts who would tell us it should be this or that. It’s less linear than even just cholesterol and I’m sure, when your doctor said ‘your cholesterol is too high’ you probably got concerned and believed them. (Mine told me mine was, at 5.6mmol/l, but, given my other measures (very low triglycides, low HbA1c, fit, low blood pressure, pulse etc) there is no scientific basis to say I’m at any risk at all but the ‘QRisk’ calculator says so so it must be right.)  So, if your GP told you your amyloid/p’tau ratio indicates you are at risk of dementia, you’d be likely to believe them. After all getting Alzheimer’s has become the number one fear and fear is a great motivator to believe what you’re told will protect you. Then that magical ratio of amyloid/p’tau or whatever it might be is prone to the same ‘diagnostic creep’, increasing the current market of 10 million people with dementia to potentially many more times this deemed to be ‘at risk’ of dementia.

This is what we need to be prepared for. It reminds me of what Peter Rost, former Vice President at Pfizer, said “I worked at Pfizer for 17 years, We didn’t discover drugs – we discovered markets. If a drug cured asthma in three days we’d kill it. Chronic disease is where the money is. Cures are bad for business.”

References

[1] Smith AD, Refsum H. Homocysteine, B Vitamins, and Cognitive Impairment. Annu Rev Nutr. 2016 Jul 17;36:211-39. doi: 10.1146/annurev-nutr-071715-050947. PMID: 27431367; see also LiJ-G,ChuJ,BarreroC,MeraliS,Pratico`D.2014.Homocysteine exacerbatesβ-amyloid, tau pathology, and cognitive deficit in a mouse model of Alzheimer’s disease with plaques and tangles. Ann. Neurol. 75:851–63; see also Shirafuji N et al Homocysteine Increases Tau Phosphorylation, Truncation and Oligomerization. Int J Mol Sci. 2018 Mar 17;19(3):891. doi: 10.3390/ijms19030891. PMID: 29562600; PMCID: PMC5877752; see also Bossenmeyer-Pourié C et al. N-homocysteinylation of tau and MAP1 is increased in autopsy specimens of Alzheimer’s disease and vascular dementia. J Pathol. 2019 Jul;248(3):291-303. doi: 10.1002/path.5254. Epub 2019 Mar 19. PMID: 307349

[2] Miller JW, McCaddon A, Yu JT, Hooshmand B, Refsum H, Smith AD. Concerning the debate about homocysteine, B vitamins, and dementia. J Alzheimers Dis. 2025 Aug;106(3):920-924. doi: 10.1177/13872877251350297. Epub 2025 Jun 23. PMID: 40551597; PMCID: PMC12284325.

[3] Tsiachristas A, Smith AD. B-vitamins are potentially a cost-effective population health strategy to tackle dementia: Too good to be true? Alzheimers Dement (N Y). 2016 Aug 11;2(3):156-161. doi: 10.1016/j.trci.2016.07.002. PMID: 29067302; PMCID: PMC5651357.

[4] Carter S, Hill AM, Yandell C, Wood L, Coates AM, Buckley JD. Impact of dietary cholesterol from eggs and saturated fatThere are many different types of fats; polyunsaturated, monounsaturated, hydrogenated, saturated and trans fat. The body requires good fats (polyunsaturated and monounsaturated) in order to… on LDL cholesterolLDL is short for low density lipoprotein. It is the “bad cholesterol” which collects in the walls of blood vessels, causing blockages. High LDL levels… levels: a randomized cross-over study. Am J Clin Nutr. 2025 Jul;122(1):83-91. doi: 10.1016/j.ajcnut.2025.05.001. Epub 2025 May 6. Erratum in: Am J Clin Nutr. 2025 Dec;122(6):1873. doi: 10.1016/j.ajcnut.2025.10.009. PMID: 40339906.

[5] Egg Consumption and the Incidence of Alzheimer’s Disease: Insights From the Adventist Health Study-2 Cohort Linked With Medicare Data, Oh, Jisoo et al. Current Developments in Nutrition, Volume 9, 107060

[6] Wang J, Huang S, Lan G, Lai YJ, Wang QH, Chen Y, Xiao ZS, Chen X, Bu XL, Liu YH, Zeng F, Zhang L, Li A, Cai Y, Sun P, He Z, Doré V, Fripp J, Bourgeat P, Chen Q, Yu JT, Tang Y, Zetterberg H, Masters CL, Guo T, Wang YJ; Translational Biomarker Research of AgIng and Neurodegeneration (TBRAIN). Diagnostic accuracy of plasma p-tau217/Aβ42 for Alzheimer’s disease in clinical and community cohorts. Alzheimers Dement. 2025 Mar;21(3):e70038. doi: 10.1002/alz.70038. PMID: 40156286; PMCID: PMC11953589.

[7]Petersen RC, Zetterberg H. A Test of the Alzheimer Disease Framework—Did It Pass? JAMA Neurol. Published online December 15, 2025. doi:10.1001/jamaneurol.2025.4966

[8] See https://www.gov.uk/government/publications/freedom-of-information-responses-from-the-mhra-week-commencing-23-may-2022/freedom-of-information-request-on-funding-and-contributions-from-pharmaceutical-companies-foi-22702; also https://change.nhs.uk/en-GB/ideas/mhra-funding; also https://www.ncbi.nlm.nih.gov/search/research-news/17133/; also https://www.nytimes.com/2022/09/15/health/fda-drug-industry-fees.html

[9] Stone J, Mitrofanis J, Johnstone DM, Robinson SR. The Catastrophe of Intracerebral Hemorrhage Drives the Capillary-Hemorrhage Dementias, Including Alzheimer’s Disease. J Alzheimers Dis. 2024;97(3):1069-1081. doi: 10.3233/JAD-231202. PMID: 38217606.

[10] Smith AD. Anti-amyloid trials raise scientific and ethical questions. BMJ. 2021 Mar 26;372:n805. doi: 10.1136/bmj.n805. PMID: 33771816.