Protein biomarkers predict dementia 15 years before diagnosis in new study

Protein biomarkers predict dementia 15 years before diagnosis in new study(warwick.ac.uk)

225 points by ao98 2 years ago | 47 comments

bglazer 2 years ago |

One caveat is that this is necessarily a retrospective study. The authors looked at historical data from the UK Biobank, ran a regression, and found these genes. So, it’s not really clear if these genes are actually causing dementia, or if they’re just related to a common cause, or (most likely) tied together through some very complicated web of biological mechanisms.

That said, they’re interesting genes. GFAP is expressed in astrocytes, which are glial cells. These perform a lot of tasks in the brain, but they seem important in protecting neurons from toxic stresses. So, this may give us some additional insight into the role of glial cells like astrocytes in dementia.

rwmj 2 years ago | |

If it's predictive, does it matter?

pama 2 years ago | | |

Yes it does. Think of typical notions of statistical significance when testing one new idea prospectively, say the concept of a p-value, or the AUC used in the paper. Now think instead of a rich dataset and you are free to fish for any of the possibly tens of thousands of signals for one signal or a combination of signals that match your result. Loosely speaking you are overfitting and the threshold for being surprised or having statistical significance is now much more strict.

https://en.wikipedia.org/wiki/Bonferroni_correction

Fluorescence 2 years ago | | |

I guess one issue is that our environment changes so that what was predictive for the past isn't for the present day.

Can gene expression be affected by pollutants more common decades ago like abestos, coal-dust or leaded petrol? It would be frustrating to only discover this in 15 years time.

Maxion 2 years ago | |

But it is not a retrospective study? They took blood samples at baseline from all participants, and later on some developed dementia?

bglazer 2 years ago | | |

For this to be prospective rather than retrospective, they would have developed the risk model beforehand.

buyohmarkers 2 years ago |

GFAP as dementia biomarker isn't a new discovery. Here's a 2023 meta-analysis that used papers as old as 2020.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10177296/

mbreese 2 years ago | |

> Proteins (for example Glial Fibrillary acidic protein, GFAP) had previously been identified as potential biomarkers for dementia in smaller studies, but this new research was much larger and conducted over several years.

The article (University press release) does mention this... but seeing a known suspect in the biomarker list would lend some confidence to any novel biomarkers found. So, it's good to see multiple studies having similar hits.

buyohmarkers 2 years ago | | |

Totally a good thing. There's a very long list of biomarker failures, and there's lots of analysis into why so many biomarkers fail in clinical applications.

One starting point for reading: https://academic.oup.com/clinchem/article/59/1/202/5622131

rablackburn 2 years ago | |

They mention this in the article, and of course, the scientific method means we _want_ to have more than one suggestive meta-analysis before we declare any kind of "discovery" at all.

elromulous 2 years ago |

https://www.nature.com/articles/s43587-023-00565-0

^ direct link to the paper.

ncr100 2 years ago | |

"... plasma proteins, GFAP, NEFL, GDF15 and LTBP2 consistently associated most with incident all-cause dementia (ACD), Alzheimer’s disease (AD) and vascular dementia (VaD), and ranked high in protein importance ordering."

xkgt 2 years ago |

> Of 1,463 proteins analysed, aided by with a type of artificial intelligence known as machine learning, 11 proteins were identified and combined as a protein panel, which the researchers have shown to be highly accurate at predicting future dementia.

I understand that press releases are intended for non-technical folks but I don't get the point of this description. Is it assumed that machine learning is less understood than artificial intelligence?

sr-latch 2 years ago | |

a scientists view of the common man's knowledge is very distorted

owenpalmer 2 years ago |

It's always encouraging to see progress in disease prevention. As a young person, I'm looking forward to what the medical field will be like when I'm 70.

ekianjo 2 years ago | |

its not disease prevention its correlation.

thfuran 2 years ago | | |

Finding a novel correlate that precedes the other observed effects of the disease in question is progress in prevention.

m3kw9 2 years ago |

Now is there something that can be done early or is it 15 extra years of suffering

berdon 2 years ago | |

From what I understand, the medicine available is fairly successful at staving off further disease progression but the normal late stage diagnosis often means it’s far too late. This might make outcomes significantly better if it works as well as reported.

carbocation 2 years ago | | |

That is true for some diseases but not all. I don't think we know how to prevent dementia. But identifying biomarkers is useful, at the very least for selecting people for enrollment in future trials.

ekianjo 2 years ago | | |

the medicine available is just cherry picking clinical trial results to make it look better than placebo but it hardly does anything

stubish 2 years ago | |

The article states there are medications that can slow or reverse the disease, if the disease is diagnosed early enough.

"An early diagnosis is critical for those with dementia. New drug technology can slow, or even reverse the progress of Alzheimer’s, but only if the disease is detected early enough. The drug lecanemab is one of two new treatments for the disease."

hgomersall 2 years ago | |

Probably diet and exercise. Would be interesting to see an interventional study based on this.

saiya-jin 2 years ago | | |

Sleep, maybe meditation, keep learning new challenging stuff (within given cognitive possibilities).

Brain is a 'muscle' so keep pushing at it, continuously, you can only help it.

quickthrower2 2 years ago |

I wonder what kinds of useful stuff dogs can smell already… but they can’t say anything!

johnnyanmac 2 years ago | |

The most common but always impressive story I hear is that some dogs can smell cancer developing months or even a year before an official diagnosis. It honestly makes me wonder if the true next step for medical tooling should focus on enhancing human smell instead of sight to expand our spectrum or magnify microbes.

as another random trivia, many animals can often feel or hear an earthquake minutes to days in advance, demonstrated by unusual behavior. This is even less consistent but a phenomenon observed for millenia (wheras we didn't even properly name understand cancer until a few centuries at best).

xattt 2 years ago | | |

> enhancing human smell

Is this not a form of spectroscopy?

loceng 2 years ago |

Are these protein biomarkers also associated with inflammation in the body, perhaps diet-specific inflammation?

foolfoolz 2 years ago |

great step to figuring how we can prevent / cure these protein changes

r-bryan 2 years ago | |

OK, but I'd rather prevent/cure the dementia.

downrightmike 2 years ago | | |

Is no one going to tell him? Should we?

megamix 2 years ago |

Does this mean that big pharma can celebrate and sell more drugs?

ransom1538 2 years ago |

I can't wait until we all find out it is from dentists or people picking their noses.

hanniabu 2 years ago | |

Why would it be from dentists?

ransom1538 2 years ago | | |

prions "Oral manifestations are rare. Evidence suggests that the risk of transmission and acquisition of a prion infection as a result of dental treatment is rare, if appropriate infection control measures are maintained."

https://www.sciencedirect.com/science/article/abs/pii/S00028...

nose picking https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10669446/