Disappointingly, the latozinemab trial for FTD-GRN failed to meet clinical endpoints (tinyurl.com/5f33sd88). However, the biomarker endpoint of elevated plasma PGRN was achieved. Perhaps PGRN localization to the lysosome, not extracellular fluids, is more critical for FTD-GRN (see PMID: 39565694).

Fantastic development from AC Immune: 2 promising small molecules for detecting TDP-43 pathology using PET imaging. There's currently no way to detect TDP-43 pathology in living patients with dementia or ALS. Could have a huge impact on future clinical trials. pmc.ncbi.nlm.nih.gov/articles/PMC...

Excellent reporting from Corinne Purtill on frontotemporal dementia. "When someone is not who they were, think neurology before psychology” www.yahoo.com/news/article...

Excellent reporting from NYT on the science of diagnosing CTE (and other tauopathies) in postmortem brain. www.nytimes.com/interactive/... 🧪

Fantastic story about how NIH funding helped transform an unexpected hypothesis into a scientific breakthrough and a successful commercial biomarker assay for the diagnosis of Parkinson's disease and related disorders: www.ninds.nih.gov/about-ninds/75th-anniversary/cnd-life-sciences 🧪

Over 3 decades of NIH-supported research enabled the FDA approval of Tofersen (Qalsody®), offering new hope for people with SOD1-related ALS. This breakthrough was made possible by unwavering, long-term societal commitment! Timeline here: www.ninds.nih.gov/about-ninds/...

Progress with rapid & accessible biomarkers of neurodegeneration! Fujirebio received FDA clearance for a blood assay that predicts amyloid plaque pathology associated with Alzheimer's disease. The assay measures the plasma ratio of pTau217:β-Amyloid1-42. www.fujirebio.com/en-us/news-e... 🧪

Fantastic series on the genetics of ALS from @thelancetneuro.bsky.social. Understanding these genetic subtypes will help therapeutic development for ALS and FTD. tinyurl.com/544kx3fu

We are so excited for this year's AFTD Education conference! Come meet us in person, this Thursday and Friday. We have a table! See you all there ❤️ @theaftd.bsky.social #curemaptftd #maptftd #ftd

We need biomarkers to detect TDP-43 loss-of-function in plasma! This will make earlier therapeutic interventions possible for many neurodegenerative diseases. Here's a funding opportunity from AMP ALS if you have a great idea: fnih.org/wp-content/u...

What's the easiest thing a 50+ yo could do to decrease their chances of getting dementia? getting the shingles vaccine! ~20% reduction over 7 years. Given the current lack of treatment/prevention options, this is a big reduction. www.nytimes.com/2025/04/02/h...

Exciting back-to-back papers in @cp-neuron.bsky.social ! The combined work supports a prion-like mechanism for TDP-43 aggregation and cell-to-cell transfer. Once initiated, aggregated TDP-43 triggers LOF and GOF events. www.cell.com/neuron/fullt... www.cell.com/neuron/fullt...

A patient was diagnosed with corticobasal syndrome. BUT, neuropath exam showed frontotemporal atrophy with a-synuclein glial cytoplasmic inclusions and neuronal cytoplasmic inclusions. By cryoEM, the a-syn fibers look just like MSA fibers. Authors conclude "FTLD-synuclein" is a rare MSA subtype

The false morel mushroom is a suspect in this Swiss ALS cluster mystery. www.theatlantic.com/health/archi...

Genetic carriers of a variant of early-onset Alzheimer's disease who were treated for 8 years (avg.) with an amyloid beta-directed antibody called gantenerumab had a 50% reduction in developing cognitive symptoms. 🧪 medicine.washu.edu/news/anti-am...

NfL beats GFAP in a head-to-head FTD biomarker competition. Gendron et al. show plasma GFAP and NfL correlate with FTD disorder severity; however, NfL outperforms GFAP as a prognostic biomarker and potential susceptibility marker. molecularneurodegeneration.biomedcentral.com/articles/10....

Super happy to announce the latest work from my lab together with Hemali Phatnani @nygenome.org & NYGC ALS Consortium! We've combined ALS patient profiling (100s!), ML classifiers and matched bulk/single-cell data to dive into ALS Molecular Subtypes #NIHfundedResearch www.cell.com/cell-reports...

Everything ALS is developing a study for monitoring and early detection of motor and speech changes. They're looking for participants who are gene carriers of ALS and are currently Asymptomatic. www.everythingals.org/asymptomatic...

Fantastic funding opportunity from AFTD to develop biomarkers for FTLD! $250,000 - $700,000 for 2 years! Better biomarkers will make diagnosis faster and help get patients into clinical trials. www.theaftd.org/for-research...

Fantastic funding opportunity from @theaftd.bsky.social to develop biomarkers for FTLD! $250,000 - $700,000 for 2 years! Better biomarkers will make diagnosis faster and help get patients into clinical trials. Please apply! www.theaftd.org/for-research...

A reminder of the significance of multi-pathology in neurogenerative disorders. Imaging and fluid biomarkers are needed for clinical trial stratification.

A two-and-a-half-year-old girl shows no signs of a rare genetic disorder, after becoming the first person to be treated for the motor-neuron condition while in the womb. https://go.nature.com/41rTube

Check out our new review of C9orf72 ALS in @thelancetneuro.bsky.social with Sarah Mizielinska, Rosa Rademakers and others! Was fun to co-write but tough to collate such incredible progress into a one article: authors.elsevier.com/c/1ke765FFzL...

Wow! Could be huge for biomarkers. AI tool uses six machine-learning models to analyze gene sequences encoding key regions in B-cell and T-cell receptors and pick out patterns associated with particular diseases.

A patient with a PSEN2 mutation should have had early dementia onset but didn't! Despite a high amyloid plaque burden there was limited tau pathology. Authors suggest tau pathology is the driver of dementia onset. Putative protective gene variants: FAM1515B, CEP290, GPCPD1, PRICKLE3, ANKRD36C.

Really appreciated Mike's expertise on NIH policies.

Excellent summary of potential therapeutic development for frontotemporal dementia resulting from granulin mutations. www.nature.com/articles/s41587-025-02562-7

"Drug commercialization cannot exist unless basic research takes place... the most financially and clinically successful drugs weren’t discovered with a specific application in mind. Instead, they emerged from fundamental scientific inquiry." www.linkedin.com/feed/update/...

Intriguing biomarker data using the NULISA platform on 86 ALS plasma samples. As expected, NEFL levels were higher in ALS samples, but tau and phospho-tau species (pTau181, pTau217, pTau231) were also elevated relative to healthy controls. onlinelibrary.wiley.com/doi/epdf/10....

The Penn FTD Center's fifth annual familial conference, Uncovering the Genetics of Familial FTD/ALS, will take place virtually in two weeks on Tuesday, February 25, 2025, from 3:00PM-6:00PM EST. Register now by clicking the button below👇 www.pennmedicine.org/FTDCFamilialConference2025

Lifetime risk of dementia projected to be 42%. 1M US adults predicted to develop dementia each year by 2060. We need faster therapeutic progress. www.nature.com/articles/s41...

What if the mechanism of Alzheimer's disease-causing mutations is stalling the γ-secretase Enzyme-Substrate complex? The “stalled complex hypothesis” suggests that γ-secretase activators (GSAs) that rescue stalled E-S complexes offer a therapeutic strategy. elifesciences.org/reviewed-pre...

Randomly assigned Parkinson’s patients took exenatide, a relative of Ozempic, but showed no benefit or slowing of the degenerative disease after 2 years www.nytimes.com/2025/02/04/h...

TDP-43 nuclear retention is antagonized by hypo-phosphorylation of its C-terminus in the cytoplasm | Communications Biology www.nature.com/articles/s42...

Beautiful new work from the Young-Pearse lab showing again the power of stem cell models in revealing mechanisms of disease AND resilience

#Alzheimers disease linked to viral #immune response in #brain. In PNAS Journal Club: www.pnas.org/post/journal... #dementia #HerpesVirus #AmyloidBeta #tau #neurodegeneration #HSV1

First Post on Blue Sky promoting science from the group! Delighted for the first Neurodegeneration paper from my lab. Led by Hammad Khan and wonderful collaborators, we reveal cortical circuit biomarkers delineating the gradual progression of Lewy pathology across synucleinopathies rdcu.be/d5f3w

.#Vaccines, antibiotics, antiviral medications and anti-inflammatory drugs are all associated with a reduced risk of #dementia. www.upi.com/Health_News/...

Executive order that pauses new grants.. www.nytimes.com/live/2025/01...

Long, but good article. Reminder that we should consider insentive structures in the scientific enterprise. www.nytimes.com/2025/01/24/o...

An analysis of prescribed drugs and dementia risk found decreased risk of dementia associated with antimicrobial and anti-inflammatory drugs. Association doesn't mean causation, but the results are intriguing, nonetheless. pmc.ncbi.nlm.nih.gov/articles/PMC...

“The impact of the collective executive orders and directives appears devastating.” scim.ag/40ureTO

This past July, the National Plan to End Parkinson’s Act became law. The NIH will be implementing this plan, which will accelerate the development of treatments and preventions for the millions of people affected by Parkinson’s disease and related disorders. www.ninds.nih.gov/news-events/...

Great science writing from Virginia Hughes on the very inspiring Linde Jacobs! www.nytimes.com/2024/12/22/h...

Our consultative peer review process means you can spend less time responding to confusing or conflicting suggestions. Learn more about peer review at eLife: https://buff.ly/4fYU4Ch

If you’re a researcher, you know that you’re much more likely to disprove your hypothesis than validate it, but there aren’t a lot of incentives to go out and publish your failed experiments. One journal is trying to change that attitude.