Clayton Mansel

Alzheimer's Association Clinical Practice Guideline on the use of blood‐based biomarkers in the diagnostic workup of suspected Alzheimer's disease within specialized care settings OBJECTIVE AND SCOPE A panel of clinicians, subject-matter experts, and guideline methodologists convened by the Alzheimer's Association conducted a systematic review and formulated evidence-based re...

New guidelines out from @alzassociation.bsky.social
on the use of blood-based biomarkers.

Disappointing that they are for memory centers and not primary care where I think they have the most utility helping docs triage patients for referral

alz-journals.onlinelibrary.wiley.com/doi/10.1002/...

Come check out poster #745 at #AAIC and learn about how a healthy lifestyle can mitigate genetic predisposition to Alzheimer’s Disease!

There are tradeoffs in these GWAS methodological choices. I argue you can either optimize for discovery and hypothesis generation (maybe reasonable for basic science pursuits) or you optimize for precision for clinical models. Thus far AD GWAS have chosen the former.

Benchmarking Alzheimer's disease prediction: personalised risk assessment using polygenic risk scores across various methodologies and genome-wide studies - PubMed Our work benchmarks the best PRS derivation and modelling strategies for AD genetic prediction.

Does this noise matter? For genomic medicine, we argue yes (example: polygenic scores).

See recent benchmarking study showing the single most important method decision was the choice of GWAS summary statistics!

pubmed.ncbi.nlm.nih.gov/39762974/

Takeaway: genetic association with AD are downwardly biased when you design your study with proxy cases, young controls, and individuals from biobanks with a history of AD compared to incident cases which was our "gold standard"

We show that the effect size for APOE's association with AD is smaller when you look at proxy cases or individuals who enroll in biobanks with a history of AD in their EHR records even though they must not have cognitive impairment to consent to the study (??) (i.e., 'prevalent')

We show that while these choices have increased the statistical power of recent AD GWAS, they have also potentially distorted the effect size of AD genetic associations. Here you can see effect size modification from different age cut-offs in the controls for example:

1) The use of non age-matched controls 2) prevalent cases in biobanks such as UKB and AoU and 3) proxy case labelling based on family history of disease

Downward bias in the association between APOE and Alzheimer’s Disease using prevalent and by-proxy disease sampling in the All of Us Research Program Background Recent genome-wide association studies (GWAS) for Alzheimer’s Disease and related dementias (ADRD) have increased statistical power via larger analysis datasets from biobanks by 1) includin...

Link: doi.org/10.1101/2025...

Fundamental to the use of genomics in medicine are the methods we use to infer an association between a variant/gene and a disease. We put recent method choices in AD genetic research to the test including...

🎉📄Excited to share a pre-print of my most recent PhD project: "Downward bias in the association between APOE and Alzheimer’s Disease using prevalent
and by-proxy disease sampling in the All of Us Research Program" (short summary and link in replies ⬇️)

Jeremy in the trenches fighting for all of us! 👏

Really excellent keynote speaker @bionexuskc.bsky.social by Dr. Tatonetti and well said - “observation is the starting point of biological discovery.”

Congrats to @claytonmansel.bsky.social for his Nexus informatics poster receiving an honorable mention. @bionexuskc.bsky.social

1 hour headways for non-Max routes OOF 🤦‍♂️

Federal Judge Extends TRO Against NIH Cap On Indirect Cost Payments Federal Judge Angel Kelly has extended her temporary hold on NIH's plan to cap its payment of indirect research grant costs to 15%.

Federal judge Angel Kelly has extended her hold on the NIH's overhead cut.

www.forbes.com/sites/michae...

Just watched Secretary Kennedy's Speech to HHS Employees.

Key takeaways:

(1) NO ANNOUNCEMENT OF FIRINGS!

(2) Generally positive tone about science and scientists

(3) Set up some strawmen about lack of transparency but promising a new era of transparency

1/2

If you wanted to cut waste, fraud, and abuse, you would empower the inspectors general.

If you wanted more waste, fraud, and abuse, you would fire them.

Defying defiance to the laws. Good for NIH!

This administration is determined to implement their priorities in the most bad-faith, disruptive way possible. If we are all about “merit” now why not just merge the Diversity F’s with the others? Ridiculous

The CSR comm I'm on just pulled all Diversity F grants from the current review cycle. These apps are reviewed alongside (and by the same criteria) as all other F grants. So, instead of helping these trainees, they will actually be punished by having their grant reviews delayed at least 1 cycle !?!?

I typed “Super Bowl Watch Party” 🤦‍♂️

Totally normal stuff here

The Trump Administration Appears to Be Holding the NIH Hostage Splinter is your home for news and opinions that challenge power in our political and economic system that's becoming more unhinged each and every day.

The Trump Administration Appears to Be Holding the NIH Hostage www.splinter.com/the-trump-ad...

Hi, Vox reporter here: If you've had a study section, NIH travel, or other NIH-related meeting cancelled (or not), raise your hand! Reply or DM me, and repost for visibility if you're able.

#academicsky @drugmonkey.bsky.social

This going to be so good and probably one of the most useful streetcar routes in the U.S. Can’t wait to ride!

We are absolutely swooning over these pics of #kcstreetcar 807 rolling through the Plaza on its 1st ever test run. 😍

One day, one toe in the water with Ambient AI Scribes. Interesting. I did not find it to be a game changer for documentation burden, but perhaps it is a paradigm shift back to being able to capture patient stories with detail and expressivity in a way busy clinicians may struggle to do. 9/x

Thus, I think you could make a strong argument that even simple data collected at primary care visits could be influencing our AD clinical trials, inflating the type II error rate. We therefore call for a more precision-trial approach matching therapies with specific clinical profiles. #Neurology

One of the coolest things we found was that the magnitude of the difference in CDR at visit 3 between the substance use history and cardiovascular history (0.45) was the same as reported in the Lecanemab trial!