Frank Shewmaker
@frank-shewmaker.bsky.social
https://www.linkedin.com/in/frank-shewmaker-53315838/
Looking for ideas to better identify, prevent & treat dementia
Looking for ideas to better identify, prevent & treat dementia
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).
Alector Announces Topline Results from Latozinemab Phase 3 Trial in Individuals with Frontotemporal Dementia Due to a GRN Mutation and Provides Business Update
SOUTH SAN FRANCISCO, Calif., Oct. 21, 2025 (GLOBE NEWSWIRE) -- Alector, Inc. (Nasdaq: ALEC), a clinical-stage biotechnology company focused on developing...
tinyurl.com
October 30, 2025 at 2:54 PM
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...
pmc.ncbi.nlm.nih.gov/articles/PMC...
October 28, 2025 at 8:46 PM
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...
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...
'I lost me': How frontotemporal dementia changed a mind and a marriage
A Westlake Village man living with frontotemporal dementia has something few people with the condition do: the ability to describe his disease.
www.yahoo.com
September 12, 2025 at 8:38 PM
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/... 🧪
www.nytimes.com/interactive/... 🧪
Gunman in Manhattan Shooting Claimed to Have CTE. How Do Doctors Search for It? (Gift Article)
summary
www.nytimes.com
September 9, 2025 at 2:06 PM
Excellent reporting from NYT on the science of diagnosing CTE (and other tauopathies) in postmortem brain.
www.nytimes.com/interactive/... 🧪
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 🧪
A Breakthrough Beneath the Skin
How a bold idea and smart federal investment created jobs, built a company, and is helping diagnose Americans in all 50 states.
www.ninds.nih.gov
August 8, 2025 at 2:59 PM
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/...
Timeline here: www.ninds.nih.gov/about-ninds/...
Tofersen (Qalsody®) - Amyotrophic Lateral Sclerosis
Amyotrophic lateral sclerosis (ALS) is a progressive and ultimately fatal neurodegenerative disorder that affects motor neurons responsible for initiating and controlling voluntary muscle movement and...
www.ninds.nih.gov
July 25, 2025 at 1:39 PM
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/...
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...
🧪
www.fujirebio.com/en-us/news-e...
🧪
May 19, 2025 at 1:25 PM
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...
🧪
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
tinyurl.com/544kx3fu
May 1, 2025 at 3:47 PM
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
tinyurl.com/544kx3fu
Reposted by Frank Shewmaker
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
@theaftd.bsky.social
#curemaptftd #maptftd #ftd
April 30, 2025 at 9:56 PM
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
@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...
fnih.org/wp-content/u...
April 8, 2025 at 3:03 PM
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...
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...
www.nytimes.com/2025/04/02/h...
Shingles Vaccine Can Decrease Risk of Dementia, Study Finds (Gift Article)
A growing body of research suggests that preventing the viral infection can help stave off cognitive decline.
www.nytimes.com
April 2, 2025 at 3:52 PM
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...
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...
www.cell.com/neuron/fullt...
www.cell.com/neuron/fullt...
Seeded aggregation of TDP-43 induces its loss of function and reveals early pathological signatures
TDP-43 pathology characterizes neurodegenerative diseases. Scialò et al. use in vitro-generated
and patient-derived TDP-43 aggregates as seeds to show that seed-induced TDP-43 cytoplasmic
aggregation ...
www.cell.com
March 31, 2025 at 8:53 PM
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...
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
Identical Seeding Characteristics and Cryo-EM Filament Structures in FTLD-Synuclein and Typical Multiple System Atrophy pubmed.ncbi.nlm.nih.gov/40135351/ #cryoem
March 28, 2025 at 1:32 AM
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...
www.theatlantic.com/health/archi...
An ‘Impossible’ Disease Outbreak in the Alps
In one tiny town, more than a dozen people were diagnosed with the rare neurodegenerative disease ALS. Why?
www.theatlantic.com
March 24, 2025 at 6:56 PM
The false morel mushroom is a suspect in this Swiss ALS cluster mystery.
www.theatlantic.com/health/archi...
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...
medicine.washu.edu/news/anti-am...
Anti-amyloid drug shows signs of preventing Alzheimer’s dementia | WashU Medicine
Clinical trial of people destined to develop early-onset Alzheimer’s disease shows eliminating amyloid from brain may prevent symptoms, supports need for confirmatory studies
medicine.washu.edu
March 21, 2025 at 12:34 PM
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...
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....
molecularneurodegeneration.biomedcentral.com/articles/10....
Comprehensive cross-sectional and longitudinal comparisons of plasma glial fibrillary acidic protein and neurofilament light across FTD spectrum disorders - Molecular Neurodegeneration
Background Therapeutic development for frontotemporal dementia (FTD) is hindered by the lack of biomarkers that inform susceptibility/risk, prognosis, and the underlying causative pathology. Blood gli...
molecularneurodegeneration.biomedcentral.com
March 17, 2025 at 3:54 PM
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....
molecularneurodegeneration.biomedcentral.com/articles/10....
Reposted by Frank Shewmaker
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...
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...
ALS molecular subtypes are a combination of cellular and pathological features learned by deep multiomics classifiers
O’Neill et al. present a deep exploration of molecular subtypes in ALS postmortem
tissues from the NYGC ALS Consortium. Matched bulk and single-cell profiles demonstrate
that ALS subtypes are a combin...
www.cell.com
March 10, 2025 at 9:49 PM
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...
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...
www.everythingals.org/asymptomatic...
March 7, 2025 at 1:56 PM
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...
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...
www.theaftd.org/for-research...
March 5, 2025 at 1:57 PM
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...
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...
www.theaftd.org/for-research...
FTD Biomarkers | AFTD
See Active FTD Biomarkers Initiative Award Recipients
www.theaftd.org
March 5, 2025 at 1:53 PM
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...
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.
Excited to see this review of tau and TDP-43 come out, great to work with @lemwisse.bsky.social
@relajoie.bsky.social and Bill Jagust 🤩🎉
alz-journals.onlinelibrary.wiley.com/doi/10.1002/...
@relajoie.bsky.social and Bill Jagust 🤩🎉
alz-journals.onlinelibrary.wiley.com/doi/10.1002/...
February 26, 2025 at 2:24 PM
A reminder of the significance of multi-pathology in neurogenerative disorders. Imaging and fluid biomarkers are needed for clinical trial stratification.
Reposted by Frank Shewmaker
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
https://go.nature.com/41rTube
Rare genetic disorder treated in womb for the first time
Nature - The child, who is now almost three years old, shows no signs of the often fatal motor neuron disease.
go.nature.com
February 23, 2025 at 11:46 AM
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
https://go.nature.com/41rTube
Reposted by Frank Shewmaker
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...
February 21, 2025 at 9:56 AM
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.
In a study involving >500 people, the AI identified a range of infections and health conditions, as well as whether participants had received a flu vaccine.
https://go.nature.com/4gPUpGT
https://go.nature.com/4gPUpGT
AI tool diagnoses diabetes, HIV and COVID from a blood sample
‘One-shot’ approach that uses machine learning to screen immune cells could help to detect conditions with overlapping symptoms.
go.nature.com
February 21, 2025 at 12:10 AM
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.
A man who seemed genetically destined to develop Alzheimer’s disease while still young has reached his mid-70s without any cognitive decline ― in only the third recorded case of such resistance to the disease
https://go.nature.com/4hUfvVy
https://go.nature.com/4hUfvVy
A man was destined for early Alzheimer’s ― these genes might explain his escape
Nature - Scientists identify nine genetic variants that could have helped a man avoid dementia at least two decades longer than expected.
go.nature.com
February 16, 2025 at 3:21 PM
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.