New Biomarkers for long term detection? Gfap Ltbp2

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Snavec
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New Biomarkers for long term detection? Gfap Ltbp2

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I saw this article in the Guardian https://www.theguardian.com/society/202 ... identified regarding some new biomarkers in blood that appear to be able to predict AD 10 years before symptoms. The four proteins they measure are Gfap, Nefl, GDF15, and Ltbp2. Clicking on the link labeled Nature Aging near the end of the article takes you to the actual published research. I also have a PDF of it is someone needs it.

As an asymptomatic APOE 4/4 I'm searching for a practical way to detect and measure the change in AD risk as I take steps to reduce my risk. Regular PET scans and Lumbar punctures are cost prohibitive and/or really uncomfortable. I know its early, but can any of the experts on this board weigh in on whether these biomarkers are likely to be affected by the preCODE/reCODE protocols and thus be used to measure progress (or lack thereof)?

Alternately, I've looked at Preclivity, but from earlier notes on this board it's unclear if that test just gives a positive/negative report or if it reports a 40/42 number or something like it that can be used to measure change over time?
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Re: New Biomarkers for long term detection? Gfap Ltbp2

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Snavec wrote: Wed Feb 14, 2024 11:13 am Alternately, I've looked at Preclivity, but from earlier notes on this board it's unclear if that test just gives a positive/negative report or if it reports a 40/42 number or something like it that can be used to measure change over time?
HI Snavec, Sorry, I don’t know anything about the testing for the biomarkers from the Guardian article and can’t comment on those.

Here is some information on the Preclivity result from their website. https://precivityad.com/patients. I added the bold typeface to highlight the ratio.

The PrecivityAD® Test Results and Interpretation report includes:

The Amyloid Probability Score (APS) represents the estimated likelihood from 0 (low likelihood) to 100 (high likelihood) that the patient will be amyloid positive on amyloid PET imaging based on his or her Aβ42/40 ratio, age, and ApoE profile. A positive amyloid PET scan is consistent with presence of amyloid plaques and an Alzheimer's disease diagnosis.

In addition to APS, the test report includes the patient’s Aβ 42/40 ratio and ApoE genotype results. Although each of these parameters can individually assess amyloid risk, their use in combination with the patient’s age to calculate the APS is superior, and therefore is the most important result.

The report provides a visual range of Low, Intermediate and High likelihood of amyloid plaques in the brain. In addition, the report provides an interpretation of the PrecivityAD® test, background and methods.


So it appears that you could track the likelihood of your having amyloid plaques and you could compare over time.
ReCODE and PreCODE track your progress with cognitive testing. To me, that seems more important since someone can have amyloid without having AD.
Last edited by floramaria on Thu Feb 15, 2024 8:25 am, edited 1 time in total.
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Re: New Biomarkers for long term detection? Gfap Ltbp2

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Thanks for clearing that up!
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Re: New Biomarkers for long term detection? Gfap Ltbp2

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Snavec wrote: Thu Feb 15, 2024 8:21 am Thanks for clearing that up!
You’re welcome. I just edited my previous post to add that I don’t know anything about those biomarkers in the study you linked to. It may be interesting to keep an eye on what information comes out related to them, and how useful they prove to be.
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Re: New Biomarkers for long term detection? Gfap Ltbp2

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Snavec wrote: Wed Feb 14, 2024 11:13 am I saw this article in the Guardian https://www.theguardian.com/society/202 ... identified regarding some new biomarkers in blood that appear to be able to predict AD 10 years before symptoms. The four proteins they measure are Gfap, Nefl, GDF15, and Ltbp2....
As an asymptomatic APOE 4/4 I'm searching for a practical way to detect and measure the change in AD risk as I take steps to reduce my risk.... I know its early, but can any of the experts on this board weigh in on whether these biomarkers are likely to be affected by the preCODE/reCODE protocols and thus be used to measure progress (or lack thereof)?
floramaria wrote: Thu Feb 15, 2024 8:28 am... I just edited my previous post to add that I don’t know anything about those biomarkers in the study you linked to. It may be interesting to keep an eye on what information comes out related to them, and how useful they prove to be.
Hi Chris and floramaria!

Chris, you're proving your first post, when you mentioned that you're casting a wide perimeter surveillance for AD research and prevention! I think we'd have to get a neuroscientist to reach the "expert" level on these proteins.
Next best thing might be an opinion in a Reuters story on this same research from Dr. Suzanne Schindler, MD/PhD, who has been studying ApoE and blood-based biomarkers with NIH grants at Washington University in St. Louis and is also a practicing neurologist in their Memory Clinic. I heard her enthusiasm at the AAIC2023 conference last July about the promise of blood-based biomarkers for early detection.
The researchers...found that people whose blood carried higher levels of the proteins GFAP, NEFL, GDF15 and LTBP2 were consistently more likely to have developed Alzheimer's disease, vascular dementia or dementia from any cause. People with elevated levels of GFAP were 2.32 times more likely to develop dementia, confirming findings from smaller studies that had pointed to the contribution of this protein..."Based on this study, it does seem likely that blood tests will be developed that can predict risk for developing dementia over the next 10 years, although individuals at higher risk often have difficulty knowing how to respond," said Dr. Suzanne Schindler, an Alzheimer's researcher at Washington University in St. Louis, who was not involved in the research..."This study did not include clinically available blood tests for Alzheimer disease, which likely would even better predict development of dementia due to Alzheimer’s disease," she said.
It may be that the NfL and GFAP are accurate as ways to monitor damage to neurons years after amyloid plaques have begun to rise.

Here's some quick explanations that I don't pretend to fully grasp, especially LTBP2, which I've never seen referenced in AD articles:
  • GFAP is an acronym for glial fibrillary acidic protein This is from a 2021 article in Nature, with research carefully conducted with an observational cohort in Australia of about 100 people in their late 70's (20 years older than you).
    Glial fibrillary acidic protein (GFAP) is an astrocytic cytoskeletal protein that serves as a marker of abnormal activation and proliferation of astrocytes due to neuronal damage, also known as astrogliosis....Plasma GFAP concentrations were significantly higher in the Aβ+ group (n = 33) compared to the Aβ− group (n = 63), before and after adjusting for potential risk factors, age, sex, and APOE ε4 status. [Note: 42% of those with a positive Amyloid PET scan were ApoE4 carriers, compared to 7% of those with a negative scan.] The current findings demonstrate that plasma GFAP levels are elevated in cognitively normal older adults at risk of AD. These observations suggest that astrocytic damage or activation begins from the pre-symptomatic stage of AD and is associated with brain Aβ load.
    Plasma glial fibrillary acidic protein is elevated in cognitively normal older adults at risk of Alzheimer’s disease
  • NfL (apparently the Brits spell it Nefl) is an acronym for neurofilament light chain, a protein that is a marker of injury to the axons of neurons in TBI, AD and other brain diseases.
  • GDF15 is a type of stress-response protein...GDF15 expression is markedly increased under conditions of inflammation, ischemia, hypoxia and organ damage. GDF15 is important for the regulation of angiogenesis, apoptosis, lipid metabolism and inflammation.
  • The LTBPs (or latent transforming growth factor β binding proteins) are important components of the extracellular matrix (ECM) that interact with fibrillin microfibrils and have a number of different roles in microfibril biology.
Here's an explanation of why GFAP and NfL are getting a lot of attention, using sophisticated blood analysis, published in July 2023 in the Alzheimer Association's Alzheimer's & Dementia journal:
Blood-based biomarkers of... Alzheimer's disease (AD) and related dementias...are not necessarily specific for a single pathophysiology but, as markers of neuronal injury and death, may provide predictive and staging information across dementia subtypes... Recent advances in quantification have brought at least two such biomarkers to the fore: neurofilament light chain (NfL; a biomarker of axonal injury) and glial fibrillary acidic protein (GFAP; a marker of astrocytic injury)..In this prospective investigation of 1712 cognitively healthy older adults, circulating NfL and GFAP were each associated with higher risk of dementia incidence and mortality independent of baseline demographics, body composition, lifestyle, vascular risk profile, and cardiovascular disease history. These associations were graded and additive, with the strongest associations observed when NfL and GFAP levels were simultaneously elevated. NfL was also independently associated with a faster 3-year decline in cognitive function.[/b]
Serum NfL and GFAP are associated with incident dementia and dementia mortality in older adults: The cardiovascular health study

These studies suggest why researchers all talk about "combination therapies" as being as important in AD prevention and treatment as in cancer.

Your participation in the ADRC research may well be advancing study of these proteins in blood sample you provide, since no advances in biomarker testing or understanding of how AD develops is possible without the participation of people like you in observational, imaging or clinical trials. Thank you for being an expert participant!
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Re: New Biomarkers for long term detection? Gfap Ltbp2

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I know its early, but can any of the experts on this board weigh in on whether these biomarkers are likely to be affected by the preCODE/reCODE protocols and thus be used to measure progress (or lack thereof)?
Great question. It's important to say up front that no one knows for sure but Dr. Bredesen has targeted p-Tau 17, Nfl, and GFAP. Given his previous experience with increasing brain volumetrics and decreasing abeta, he suspects that these may be markers that we can use to track progress on the protocol. He did mention that p-Tau 17 will move more slowly than abeta as it's downstream so he recommends repeating that marker annually and not sooner. I'll check on the frequency of the other two and share his response.
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Re: New Biomarkers for long term detection? Gfap Ltbp2

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Thanks, Julie. That's very encouraging.

A friend of mine founded and runs a lab and has been working with me -- he ran all the cognoscopy tests I wanted for my brother and me. I asked him about these new biomarkers and he responded that he's not sure anyone in the US is testing these markers today and noted the research was coming out of the EU. Do you know of any US labs that can test for these? Is it something a university can do? I am participating in the ADRC study at Duke and could reach out to them.

FWIW, my friend tells me he's getting ready to launch a major molecular division at his lab and could add these markers to a target list once he's launched. When that happens, I may start another thread for a wishlist of biomarkers you could get from a lab as a consumer.
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Re: New Biomarkers for long term detection? Gfap Ltbp2

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A friend of mine founded and runs a lab and has been working with me -- he ran all the cognoscopy tests I wanted for my brother and me. I asked him about these new biomarkers and he responded that he's not sure anyone in the US is testing these markers today and noted the research was coming out of the EU. Do you know of any US labs that can test for these? Is it something a university can do? I am participating in the ADRC study at Duke and could reach out to them.
Thank you for your service. Dr. Bredesen is coordinating with a neurological specialty lab and will be offering all three of these tests directly to consumers in the US shortly. I'm unsure if the tests will be offered elsewhere but will check.
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