Big thanks to all co-authors and collaborators: @RikOssenkoppele @ErikRubenSmith @LECollij @aitchbi @jorittmo @karlssonlinda1 @DaniellevWe @JakeVogel @EStomrud @SebastianPalmqv @NiklasMattsson4 @NicolaSpotorno @OskarHansson9 + those not on X.

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.

Join millions who have switched to Grok.

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/🧵 Here, we tried to disentangle whether tau asymmetry is due to reduced inter-hemispheric brain connectivity (potentially restricting tau spread), or linked to asymmetric amyloid-beta (Aβ) deposition (indicating greater hemisphere-specific vulnerability to AD pathology).

🚨New paper alert! Our study led by @teanijarv 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: A thread🧵👇.

Thanks to all coauthors: @JosephTherr , @NicholasAshton, @andrealessa, @NiklasMattsson4, @SebastianPalmqv, @EStomrud, @pedrorosaneto, and @OskarHansson9.And those not on X.

4⃣In 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.

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

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

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

🚨New publication in @NatureAging🚨.Co-led between @MontoliuGaya and @gesalbla. We measured several tau peptides in blood and assess their different relationships with Alzheimer’s disease stages. 🧵.

A huge thanks to all authors and collaborators who made this work possible! @OskarHansson9 @LECollij @_JakeVogel_ @SebastianPalmqv @FBarkhof @RikOssenkoppele and all not on X.

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%.

3/🧵In an autopsy-confirmed cohort, this two-step approach detected Lewy body pathology with 94% accuracy, while reducing the number of required CSF tests by 43%. This performance was similar compared to performing CSF SAA testing in every subject.