BREAKING! University Of Cincinnati Study Finds That Alzheimer’s Disease Is Caused By Low Levels Of Amyloid Beta Protein And Not By Amyloid Plaques!
A new study led by researchers from the University of Cincinnati-USA has found that Alzheimer’s Disease
is caused by low levels of a soluble protein called amyloid beta and not by amyloid plaques!
The study team also compromised researchers from Karolinska Institutet-Sweden, Texas Tech University-USA, University of Eastern Finland, University of Oxford-UK, Fondazione IRCCS Istituto Neurologico Carlo Besta-Italy, University of Southern California-USA, Mayo Clinic-USA, Osaka City University-Japan, German Center for Neurodegenerative Diseases-Germany and Ludwig-Maximilians University-Germany.
The study team based their study on a hypothesis that in amyloid-positive individuals at risk for Alzheimer’s disease
(AD), high soluble 42-amino acid amyloid-β (Aβ42) levels are associated with normal cognition. However, it is unknown if this relationship applies longitudinally in a genetic cohort.
The study was conducted in order to test the hypothesis that high Aβ42 preserves normal cognition in amyloid-positive individuals with Alzheimer’s disease
(AD)-causing mutations (APP, PSEN1, or PSEN2) to a greater extent than lower levels of brain amyloid, cerebrospinal fluid (CSF) phosphorylated tau (p-tau), or total tau (t-tau).
For the study, cognitive progression was defined as any increase in Clinical Dementia Rating (CDR = 0, normal cognition; 0.5, very mild dementia; 1, mild dementia) over 3 years. Amyloid-positivity was defined as a standard uptake value ratio (SUVR) ≥1.42 by Pittsburgh compound-B positron emission tomography (PiB-PET).
The study team used modified Poisson regression models to estimate relative risk (RR), adjusted for age at onset, sex, education, APOE4 status, and duration of follow-up. The results were confirmed with multiple sensitivity analyses, including Cox regression.
Of 232 mutation carriers, 108 were PiB-PET-positive at baseline, with 43 (39.8% ) meeting criteria for progression after 3.3±2.0 years.
The study findings showed that soluble Aβ42 levels were higher among CDR non-progressors than CDR progressors. Higher Aβ42 predicted a lower risk of progression (adjusted RR, 0.36; 95% confidence interval [CI], 0.19–0.67; p = 0.002) better than lower SUVR (RR, 0.81; 95% CI, 0.68–0.96; p = 0.018). CSF Aβ42 levels predicting lower risk of progression increased with higher SUVR levels.
The study findings concluded that high CSF Aβ42 levels predict normal cognition in amyloid-positive individuals with AD-causing genetic mutations.
The study findings were published in the peer reviewed Journal of Alzheimer’s Disease.
The past belief that Alzheimer’s Disease
was caused by amyloid plaque build-ups has been found to be a major fallacy after evidence emerged that the studies claiming such as hypothesis were all faked and were nothing more but an elaborat
e scam that led everything from diagnostics, drug development and treatment protocols to be built around faked study findings.
This new research from the University of Cincinnati (UC) bolsters a hypothesis that Alzheimer’s disease
is caused by a decline in levels of a specific protein.
The international study was led by UC researchers Dr Alberto Espay, MD, and Dr Andrea Sturchio, MD, in collaboration with the Karolinska Institute in Sweden and other research centers across the world.
The study was focused on a protein called amyloid-beta. The protein normally carries out its functions in the brain in a form that is soluble, meaning that it is dissolvable in water. However, it sometimes hardens into clumps, known as amyloid plaques.
Sadly, for the last few decades, the scientist and medical professionals were falsely led to believe that Alzheimer’s was caused by the buildup of amyloid plaques in the brain.
The study team however hypothesized that plaques are actually just a consequence of the levels of soluble amyloid-beta in the brain decreasing. These levels decrease because the normal protein, under situations of biological, metabolic, or infectious stress, transforms into the abnormal amyloid plaques.
Dr Espay who is also a professor of neurology in the UC College of Medicine, and director and endowed chair of the James J. and Joan A. Gardner Family Center for Parkinson’s Disease and Movement Disorders at the UC Gardner Neuroscience Institute told Thailand Medical News
, “The paradox is that so many of us accrue plaques in our brains as we age, and yet so few of us with plaques go on to develop dementia. Yet the plaques remain the center of our attention as it relates to biomarker development and therapeutic strategies.”
Hilariously, it was noted that over the years, many clinical trials and research studies have aimed at reducing amyloid plaques in the brain.
Some even succeeded in lessening plaques but in some of the clinical trials that reduced the levels of soluble amyloid-beta, patients showed worsening in clinical outcomes.
Dr Sturchio warned, “I think this is probably the best proof that reducing the level of the soluble form of the protein can be toxic. When done, patients have gotten worse.”
Dr Sturchio is also the first author of the study report and an adjunct research instructor at UC’s College of Medicine.
Past research from the team found that regardless of the buildup of plaques in the brain, individuals with high levels of soluble amyloid-beta were cognitively normal, but those with low levels of the protein were more likely to have cognitive impairment.
In the current research, the study team examined the levels of amyloid-beta in a subset of patients with mutations that predict an overexpression of amyloid plaques in the brain, which is thought to make them more likely to develop Alzheimer’s disease
Dr Sturchio said, “One of the strongest supports to the hypothesis of amyloid toxicity was based on these mutations. We studied that population because it offers the most important data.”
Interestingly, even in this group of patients thought to have the highest risk of Alzheimer’s disease
, the scientists observed similar results as the study of the general population.
Dr Espay added, “What our study found was that individuals already accumulating plaques in their brains who are able to generate high levels of soluble amyloid-beta have a lower risk of evolving into dementia over a three-year span.”
Importantly, the study findings showed that individuals can remain cognitively normal regardless of the amount of amyloid plaques in their brains as long as they maintain a baseline level of soluble amyloid-beta in the brain above 270 picograms per milliliter.
Dr Espay further added, “It’s only too logical, if you are detached from the biases that we’ve created for too long, that a neurodegenerative process is caused by something we lose, amyloid-beta, rather than something we gain ie amyloid plaques. Degeneration is a process of loss, and what we lose turns out to be much more important.”
The study team says that the research is moving forward to investigate whether increasing the levels of soluble amyloid-beta in the brain is a beneficial therapy for patients with Alzheimer’s.
Dr Espay commented that it will be essential to ensure that the elevated levels of the protein introduced into the brain do not then turn into amyloid plaques, since the soluble version of the protein is needed for normal function to make an impact in the brain.
From a macro perspective, the study team believes a similar hypothesis of what causes neurodegeneration can be applied to other diseases including Parkinson’s and Creutzfeldt-Jakob disease.
Ongoing research in these areas is proceeding as well. For instance, in Parkinson’s disease, a normal soluble protein in the brain called alpha-synuclein can harden into a deposit called a Lewy body. The study team hypothesize that Parkinson’s is not caused by Lewy bodies aggregating in the brain, but instead by a decrease in levels of normal, soluble alpha-synuclein.
Dr Espay said, “We’re advocating that what may be more meaningful across all degenerative diseases is the loss of normal proteins rather than the measurable fraction of abnormal proteins. The net effect is a loss not a gain of proteins as the brain continues to shrink as these diseases progress.”
The study team says that they envision a future with two approaches to treating neurodegenerative diseases: rescue medicine and precision medicine.
The concept of rescue medicine looks like the current work, examining whether boosting levels of key proteins like amyloid-beta leads to better outcomes.
Dr Espay added, “Interestingly, lecanemab, the anti-amyloid drug recently reported as beneficial, does something that most other anti-amyloid treatments don’t do in addition to reducing amyloid: it increases the levels of the soluble amyloid-beta.”
The study team said that the second approach involves a precision medicine approach that entails going deeper to understand what is causing levels of soluble amyloid-beta to decrease in the first place, whether it is a virus, toxin, nanoparticle, or biological or genetic process. If the root cause is addressed, the levels of the protein wouldn’t need to be boosted because there would be no transformation from soluble, normal proteins to amyloid plaques.
The study team said precision medicine would provide more personalized treatments by taking into account the fact that no two patients are exactly alike.
The study team are making progress in precision medicine through the Cincinnati Cohort Biomarker Program, a project aiming to divide neurodegenerative diseases by biological subtypes in order to match therapies based on biomarkers to those most likely to benefit from them.
Dr Espay explained, “The Cincinnati Cohort Biomarker Program is dedicated to working toward deploying the first success in precision medicine in this decade. By recognizing biological, infectious and toxic subtypes of Parkinson’s and Alzheimer’s, we will have specific treatments that can slow the progression of those affected.”
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