My 6yo daughter just asked me if, when she is a grownup and I am "very very old," I will still run my lab. I said probably yes. She then said she would run a lab with me. I asked her why not with @jplotkin? She leaned in and whispered, "Because girls just wanna have fun."

Kickoff to welcome the summer students in our lab. Are we a little anxious? No doubt. Are we eating oysters like there’s no tomorrow. That, too. Love this group, who choose to not just survive but THRIVE, in any circumstance!

ft. @gkannarkat, R. Zack, T. Skrinak, J. Morley, @R_DavilaRivera, @Sanaz_Arezouman, K. Dorfman, D. Wolk, D. Weintraub, @doctrops, @drdirwin, @alicechenp (@PennNeurology), K. Luk, @TNRLab, V. Lee (@PennPathLabMed), S. Xie & G. Chandrasekaran (@UPennDBEI) https://t.co/THBGsbd3Oa

That’s as far as we could take it b4 Hanwen Zhang moved on to her neuroscience PhD program! But now it’s more than one more point on a GWAS. We have a cell type, a pathway, found in hundreds of human samples.

We wondered, too, bc its well-characterized function in inserting tail-anchored proteins doesn’t tell us where and in what cell types in the brain you find it. So we stained 56 brains, finding that CAMLG is expressed in neurons and higher in PD. 5/n

Looked like this (lysosomal markers measured by targeted MS by our collaborator Henrik Zetterberg). What does CAMLG look like in the brain, you ask? 4/n

We found that PD risk SNPs in CAMLG and ITGA8 associated with one or more lysosomal biomarkers. 3/n

We tested PD risk variants for associations with a panel of CSF lysosomal biomarkers in 273 people, reasoning that this might link loci with a pathway implicated in disease pathogenesis. 2/n

https://t.co/DGlaKu9Xw5 Calcium modulating ligand confers risk for Parkinson's disease and impacts lysosomes - PMC Missed tweeting our March paper bc I was on a social media break. 😉 In the next installment of “trying to make sense of #Parkinsons #GWAS…” 1/n

I am trusting @gkannarkat to help me figure this out!! Stay tuned!!

And it doesn’t stop at in vitro fibrillization! Those same plasma Strain A aSyn species could also seed insoluble aSyn aggregates in cells. So many questions! Does this mean PD and DLB begin outside the brain? Where are the aSyn strains coming from? How many strains exist? 7/n

Including at an individual sample level. Just pausing to comment that PLASMA aSyn IPd with the Strain A antibody from every one of the PD individuals tested amplified by SAA. 6/n

We think so. Because they amplify in aSyn seed amplification assays. Plasma Strain A aSyn from PD in particular could seed SAAs. 5/n

In human plasma, our aSyn strain ELISAs separated (partially) #Parkinsons vs Dementia with Lewy Bodies (DLB) individuals. Which was super surprising to me, since these two conditions are indistinguishable neuropathologically. Were these aSyn plasma species doing anything? 4/n

We developed ELISAs with these mAbs, which recognize HMW aSyn in brain lysates. However, when we used the ELISAs in human CSF, we got nothing. 😨 but we happened to test human plasma at the same time… 3/n

We started with 2 mAb raised against conformations of aSyn that seed aSyn inclusion (A) vs aSyn+tau inclusions (B). Both see pathology in #Parkinsons disease brains. 2/n

Our new paper is out today! Blood α‐Synuclein Separates Parkinson's Disease from Dementia with Lewy Bodies - Kannarkat - Annals of Neurology - Wiley Online Library 1/n

https://t.co/k1YIQyWuXH Garbage In, Garbage Out - Science Friday Check out this profile of my science mom, the incomparable Virginia Lee. RT if you’ve heard her say, “Garbage in, garbage out.” 😉 @lvolpic @Roy_Lab_Thinks @MXHend @ChaoPeng19 (tag in others…)

Beyoncé’s America is the one I love with all my heart. 😍❤️ (also, happy anniversary @jplotkin 😘)

Privileged to be a physician-scientist in a time when efforts like these spanning genetics, engineering, & medicine come to fruition. Hats off to @kiranmusunuru, Rebecca Ahrens-Niklas ,@UrnovFyodor & more for this milestone in interventional genetics.

Lab dinner to say goodbye to the fantastic Eliza Brody and Carrie Lewis, both headed to Cornell (MD-Eliza and PhD-Carrie). And to celebrate Masen Boucher passing prelims with flying colors! Choosing science right now is hard… so here are also some peonies.