Cell-weighted polygenic risk scores are associated with β-amyloid and tau biomarkers in Alzheimer’s disease Kumar et al. report distinct cellular effects on measures of β-amyloid and tau. Importantly, they also found cell-level genetic evidence for a role for mic

🚨New publication in Brain Communications!
In this study led by Atul Kumar, we show that microglial cells play a key role in Alzheimer's disease, particularly in regulating changes in soluble tau, based on cell-type-specific genetic evidence.
🔗Full paper: academic.oup.com/braincomms/a...

🙏Many thanks to all collaborators in this large study including 12 international cohorts!

🎯The use of plasma p-tau217 will reduce resource demands and burdensome procedures accelerating the development and implementation of early AD therapeutics.

5️⃣ In conclusion, our results support the clinical utility of plasma p-tau217 as stand-alone tool for identifying preclinical AD but adding confirmatory CSF/PET would further improve PPVs as needed in many clinical applications.

4️⃣ Finally, in a subsample we tested whether mass-spectrometry (MS) based methods would improve the results compared to immunoassays (IA). MS showed significantly higher accuracy and sensitivity, but PPV remained comparable to that of IA.

3️⃣ In a hypothetical trial aiming to recruit 100 amyloid-positive individuals, there was >40% reduction in number of PET/CSF tests in blood-based approaches, although the initial number of individuals needed were increased.

2️⃣ Next, we investigated a 2-step approach in which 🩸p-tau217 positive individuals were confirmed with CSF or PET.
With this approach, PPV increased to over 90% while maintaining sensitivity.

1️⃣ In a sample of 2916 cognitively unimpaired individuals we found that plasma p-tau217🩸alone (single-step) was able to determine amyloid-b status with good accuracy and, most importantly, with a positive predictive value (PPV) around 80%.

Plasma P-Tau217 to Identify Preclinical AD This cohort study evaluates the use of plasma phosphorylated tau 217 in identifying preclinical Alzheimer disease in individuals with amyloid β pathology.

🚨Paper alert🚨
New publication in JAMA Neurology led by @gsalvado.bsky.social. In a multicentric study, we examined the clinical utility to assess preclinical #Alzheimer’s disease in cognitively unimpaired individuals.

jamanetwork.com/journals/jam...

A 🧵...

The study was led by PhD students Pontus Tideman and Linda Karlsson. Thank you also to all co-authors.

Primary care detection of Alzheimer’s disease using a self-administered digital cognitive test and blood biomarkers - Nature Medicine | The Swedish BioFINDER study New publication in Nature Medicine!   In this study, led by PhD students Pontus Tideman and Linda Karlsson, we demonstrate that a brief, self-administered cognitive test battery can reliably identify ...

🚨New publication in Nature Medicine!
In this study, we demonstrate that a brief, self-administered cognitive test battery can reliably identify individuals with cognitive impairment in a primary care setting.
More details: linkedin.com/feed/update/...
Full paper: www.nature.com/articles/s41...

Big thanks to all co-authors and collaborators: @rikossenkoppele.bsky.social @aitchbi.bsky.social @jorittmo.bsky.social @jwvogel.bsky.social + those not on bksy

7/🧵 These results suggest that hemispheric difference in Aβ deposition, rather than reduction in connectivity, is associated with asymmetric tau accumulation, highlighting regional vulnerability as a crucial factor in determining the distribution of AD pathology.

6/🧵 More asymmetric tau accumulation was tied to faster cognitive decline, particularly in regions affected at later disease stages.

5/🧵 Longitudinally, Aβ asymmetry at baseline predicted subsequent increase in tau asymmetry over time, especially in participants who hadn’t yet developed neocortical tau deposits. The affected Braak regions depended on disease stage and progression.

4/🧵 We replicated this Aβ-tau asymmetry link across three independent cohorts (OASIS-3, A4, ADNI), showing it is a consistent feature throughout the AD continuum.

3/🧵 There were no significant differences in inter-hemispheric connectivity (functional or structural) between asymmetric and symmetric tau groups. Instead, we observed a strong association between the laterality of Aβ and tau pathology, especially in temporal regions.

2/🧵 We assessed both inter-hemispheric brain connectivity (using RSfMRI and dMRI) and the spatial distribution of Aβ in 452 A+T+ participants from the Swedish BioFINDER-2 cohort to investigate the differences between asymmetric and symmetric tau pathology distribution.

1/🧵 In this study, we tried to disentangle whether tau asymmetry is due to reduction in inter-hemispheric brain connectivity (potentially restricting tau spread), or if it is linked to asymmetric amyloid-beta (Aβ) deposition (indicating greater hemisphere-specific vulnerability to AD pathology).

Hemispheric asymmetry of tau pathology is related to asymmetric amyloid deposition in Alzheimer’s Disease - Nature Communications Asymmetrical distribution of tau pathology in Alzheimer’s disease is linked to asymmetrical amyloid-beta deposition, not reduced brain connectivity, suggesting regional vulnerability plays a key role ...

🚨New paper alert! Our study led by @teanijarv.bsky.social
investigated why some individuals with Alzheimer’s disease (AD) develop hemispheric asymmetry in tau pathology and what drives this phenomenon.
Out now in Nature Communications! 🔗Full article: doi.org/10.1038/s414...
A thread🧵👇

A huge thanks to all coauthors!
@josephtherr.bsky.social

4️⃣In summary, we have developed a biomarker-based staging model using plasma tau biomarkers and validated in TRIAD. We believe these findings will enhance the application of blood tau biomarkers, improving patient management in both clinical trials and routine clinical practice.

3️⃣Most importantly, we also showed significant differences in longitudinal rates of change of several AD biomarkers.

2️⃣Based on the most sensitive of these markers, we developed a plasma-based staging system that showed good correlation with other AD biomarkers.

1️⃣In brief, we showed that different plasma tau biomarkers were differently associated with different clinical stages of the disease.

Plasma tau biomarkers for biological staging of Alzheimer’s disease - Nature Aging Montoliu-Gaya, Salvadó et al. develop a blood-based model using tau biomarkers measured in a single analysis enabling biological staging of Alzheimer’s disease to support the diagnosis, prognosis and ...

🚨New publication in Nature Aging🚨
Co-led between Laia Montoliu-Gaya and @gsalvado.bsky.social.
We measured several tau peptides in blood and assess their different relationships with Alzheimer’s disease stages.
nature.com/articles/s43...
🧵

A huge thanks to all authors and collaborators who made this work possible!

6/🧵Taken together, we present an accurate two-step approach for predicting LBP in the brain using a smell test followed by CSF SAA testing in smell-test positive individuals. This could minimize costs, reduce patient burden, and improve the known underdiagnosis of DLB and PD.

5/🧵These findings replicated to an in vivo cohort, where the smell-function test could predict CSF SAA status with 79% accuracy while reducing the required number of CSF tests by 26%.

4/🧵Importantly, this two-step approach worked well across multiple clinical scenarios, including individuals with clinical parkinsonism, those with an Alzheimer's-like presentation, and clinically unimpaired participants where it reduced the need of CSF testing by up to 80%.