For decades, we have tried to suppress γ-secretase, lower Aβ42 levels, or remove amyloid from the brain. We show that PSEN1 mutations already reduce γ-secretase activity and lower Aβ42. Why restoring Aβ42 is the way forward for #Alzheimers, via @Brain1878
academic.oup.com/brain/articl...
academic.oup.com/brain/articl...
Restoring amyloid-β42 and γ-secretase function in Alzheimer’s disease
Espay et al. challenge the view that Alzheimer’s disease is caused by increased gamma-secretase activity and overproduction of Aβ42. Instead, they suggest
academic.oup.com
November 6, 2025 at 7:15 PM
For decades, we have tried to suppress γ-secretase, lower Aβ42 levels, or remove amyloid from the brain. We show that PSEN1 mutations already reduce γ-secretase activity and lower Aβ42. Why restoring Aβ42 is the way forward for #Alzheimers, via @Brain1878
academic.oup.com/brain/articl...
academic.oup.com/brain/articl...
Millipore's resource, RRID:AB_94882, was just reported to be used in "Mutations in PSEN1 predispose inflammation in an astrocyte model of familial Alzheimer’s disease through disrupted regulated intramembrane proteolysis". Thank you for making your methods matter! #OpenScience #OpenScience
doi.org
February 18, 2025 at 8:01 AM
Millipore's resource, RRID:AB_94882, was just reported to be used in "Mutations in PSEN1 predispose inflammation in an astrocyte model of familial Alzheimer’s disease through disrupted regulated intramembrane proteolysis". Thank you for making your methods matter! #OpenScience #OpenScience
PSEN1-M146V and PSEN1-A246E mutations associated with Alzheimers disease impair proper microglia differentiation https://www.biorxiv.org/content/10.1101/2023.10.08.561397v1
PSEN1-M146V and PSEN1-A246E mutations associated with Alzheimers disease impair proper microglia differentiation https://www.biorxiv.org/content/10.1101/2023.10.08.561397v1
Genetic variants associated with the late onset of Alzheimers disease (AD), were correlated with gen
www.biorxiv.org
October 10, 2023 at 6:15 PM
PSEN1-M146V and PSEN1-A246E mutations associated with Alzheimers disease impair proper microglia differentiation https://www.biorxiv.org/content/10.1101/2023.10.08.561397v1
'Mutations in #PSEN1 predispose #inflammation in an #astrocyte model of familial #AlzheimersDisease through disrupted regulated intramembrane proteolysis'
Oliver J. Ziff... @selinawray.bsky.social & Charles Arber @uclqsion.bsky.social
molecularneurodegeneration.biomedcentral.com/articles/10....
Oliver J. Ziff... @selinawray.bsky.social & Charles Arber @uclqsion.bsky.social
molecularneurodegeneration.biomedcentral.com/articles/10....
Mutations in PSEN1 predispose inflammation in an astrocyte model of familial Alzheimer’s disease through disrupted regulated intramembrane proteolysis - Molecular Neurodegeneration
Background Mutations in PSEN1 cause familial Alzheimer’s disease with almost complete penetrance. Age at onset is highly variable between different PSEN1 mutations and even within families with the sa...
molecularneurodegeneration.biomedcentral.com
June 20, 2025 at 10:33 PM
'Mutations in #PSEN1 predispose #inflammation in an #astrocyte model of familial #AlzheimersDisease through disrupted regulated intramembrane proteolysis'
Oliver J. Ziff... @selinawray.bsky.social & Charles Arber @uclqsion.bsky.social
molecularneurodegeneration.biomedcentral.com/articles/10....
Oliver J. Ziff... @selinawray.bsky.social & Charles Arber @uclqsion.bsky.social
molecularneurodegeneration.biomedcentral.com/articles/10....
The Curious Case of a Heterozygous Loss-of-Function PSEN1 variant associated with Early-Onset Alzheimer’s Disease #NeuroDegeneration 🧪🧠
https://www.researchsquare.com/article/rs-7222993/latest
https://www.researchsquare.com/article/rs-7222993/latest
August 27, 2025 at 4:02 PM
The Curious Case of a Heterozygous Loss-of-Function PSEN1 variant associated with Early-Onset Alzheimer’s Disease #NeuroDegeneration 🧪🧠
https://www.researchsquare.com/article/rs-7222993/latest
https://www.researchsquare.com/article/rs-7222993/latest
There are three in our study: APP, Presenilin 1 and Presenilin 2. (PSEN1, PSEN2). His is PSEN2.
March 21, 2025 at 5:55 PM
There are three in our study: APP, Presenilin 1 and Presenilin 2. (PSEN1, PSEN2). His is PSEN2.
The study says that the catalytic effect of the PSEN1 M146L (A > C) mutation in Aβ formation is also observed outside the brain, such as in fibroblasts. It provides easy access to study the mutation, similar to brain samples. In this study, they selected CRISPR-Cas9 suitable for this mutation.
July 7, 2025 at 2:43 PM
The study says that the catalytic effect of the PSEN1 M146L (A > C) mutation in Aβ formation is also observed outside the brain, such as in fibroblasts. It provides easy access to study the mutation, similar to brain samples. In this study, they selected CRISPR-Cas9 suitable for this mutation.
(2/13) NCT01760005 was a Phase II/III trial of anti-amyloid monoclonal antibodies gantenerumab (n= 52) or solanezumab (52) vs. placebo (40) to test if either could slow cognitive decline over a mean of 5 years in individuals with a genetic mutation in APP, PSEN1, or PSEN2.
November 24, 2024 at 9:29 AM
(2/13) NCT01760005 was a Phase II/III trial of anti-amyloid monoclonal antibodies gantenerumab (n= 52) or solanezumab (52) vs. placebo (40) to test if either could slow cognitive decline over a mean of 5 years in individuals with a genetic mutation in APP, PSEN1, or PSEN2.
Delayed neurodegenerative symptoms in a PSEN2 carrier (dominantly inherited Alzheimer’s “escapee”). Despite tons of amyloid plaque, tau pathology delayed >10y. Analogous to PSEN1 patients with APOE3-Christchurch homozygosity (2019) & RELN-COLBOS (2023).
www.nature.com/articles/s41...
www.nature.com/articles/s41...
Longitudinal analysis of a dominantly inherited Alzheimer disease mutation carrier protected from dementia - Nature Medicine
A rare case of asymptomatic dominantly inherited Alzheimer’s reveals confined tau pathology and unique proteomic features, highlighting potential resilience mechanisms decades beyond expected onset.
www.nature.com
February 11, 2025 at 6:39 PM
Delayed neurodegenerative symptoms in a PSEN2 carrier (dominantly inherited Alzheimer’s “escapee”). Despite tons of amyloid plaque, tau pathology delayed >10y. Analogous to PSEN1 patients with APOE3-Christchurch homozygosity (2019) & RELN-COLBOS (2023).
www.nature.com/articles/s41...
www.nature.com/articles/s41...
🔍 Seizures & Alzheimer's: What You Need to Know
Repost this important information!
A 2021 meta-analysis reveals that seizures occur in up to 16% of people with Alzheimer’s, with rates rising to nearly 50% in cases linked to genetic mutations (APP, PSEN1, PSEN2). (1/2)
Repost this important information!
A 2021 meta-analysis reveals that seizures occur in up to 16% of people with Alzheimer’s, with rates rising to nearly 50% in cases linked to genetic mutations (APP, PSEN1, PSEN2). (1/2)
buff.ly
January 30, 2025 at 11:20 PM
🔍 Seizures & Alzheimer's: What You Need to Know
Repost this important information!
A 2021 meta-analysis reveals that seizures occur in up to 16% of people with Alzheimer’s, with rates rising to nearly 50% in cases linked to genetic mutations (APP, PSEN1, PSEN2). (1/2)
Repost this important information!
A 2021 meta-analysis reveals that seizures occur in up to 16% of people with Alzheimer’s, with rates rising to nearly 50% in cases linked to genetic mutations (APP, PSEN1, PSEN2). (1/2)
📃Scientific paper: Location of pathogenic variants in PSEN1 impacts progression of cognitive, clinical, and neurodegenerative measures in autosomal‐dominant Alzheimer's disease
➡️ Continued on ES/IODE
➡️ Continued on ES/IODE
October 13, 2024 at 7:18 AM
📃Scientific paper: Location of pathogenic variants in PSEN1 impacts progression of cognitive, clinical, and neurodegenerative measures in autosomal‐dominant Alzheimer's disease
➡️ Continued on ES/IODE
➡️ Continued on ES/IODE
In these cases, the symptoms of dementia can appear much earlier, potentially in the late 30’s to late 40’s. Early-onset Alzheimer’s is rare, affecting less than 10% of all cases. Among these, 10-15% are caused by mutations in APP, PSEN1, or PSEN2.
January 3, 2025 at 2:35 PM
In these cases, the symptoms of dementia can appear much earlier, potentially in the late 30’s to late 40’s. Early-onset Alzheimer’s is rare, affecting less than 10% of all cases. Among these, 10-15% are caused by mutations in APP, PSEN1, or PSEN2.
Dec featured dataset Kuzuya et al. Interaction between SYT1 & PSEN1 links calcium, synapse & APP PMID:27036734
ebi.ac.uk/intact/query/p…
ebi.ac.uk/intact/query/p…
IntAct Portal
EMBL-EBI
www.ebi.ac.uk
December 9, 2024 at 11:46 AM
Dec featured dataset Kuzuya et al. Interaction between SYT1 & PSEN1 links calcium, synapse & APP PMID:27036734
ebi.ac.uk/intact/query/p…
ebi.ac.uk/intact/query/p…
Excited to share our new work out in Alzheimer's Research & Therapy! We profiled FAD-causal mutations in PSEN1, PSEN2, and APP using patient-derived iPSC neurons and multiomics (RNA-seq and ATAC-seq) to ascertain regulatory mechanisms associated with disease. alzres.biomedcentral.com/articles/10....
Integrative multiomics reveals common endotypes across PSEN1, PSEN2, and APP mutations in familial Alzheimer’s disease - Alzheimer's Research & Therapy
Background PSEN1, PSEN2, and APP mutations cause Alzheimer’s disease (AD) with an early age at onset (AAO) and progressive cognitive decline. PSEN1 mutations are more common and generally have an earl...
alzres.biomedcentral.com
January 9, 2025 at 5:57 PM
Excited to share our new work out in Alzheimer's Research & Therapy! We profiled FAD-causal mutations in PSEN1, PSEN2, and APP using patient-derived iPSC neurons and multiomics (RNA-seq and ATAC-seq) to ascertain regulatory mechanisms associated with disease. alzres.biomedcentral.com/articles/10....
Alzheimer's disease induced neurons bearing PSEN1 mutations exhibit reduced excitability https://www.biorxiv.org/content/10.1101/2024.03.22.586207v1
Alzheimer's disease induced neurons bearing PSEN1 mutations exhibit reduced excitability https://www.biorxiv.org/content/10.1101/2024.03.22.586207v1
Alzheimer's disease (AD) is a devastating neurodegenerative condition that affects memory and cognit
www.biorxiv.org
March 24, 2024 at 5:29 AM
Alzheimer's disease induced neurons bearing PSEN1 mutations exhibit reduced excitability https://www.biorxiv.org/content/10.1101/2024.03.22.586207v1
Integrative multiomics reveals common endotypes across PSEN1, PSEN2, and APP mutations in familial Alzheimer’s disease
alzres.biomedcentral.com/articles/10....
alzres.biomedcentral.com/articles/10....
Integrative multiomics reveals common endotypes across PSEN1, PSEN2, and APP mutations in familial Alzheimer’s disease - Alzheimer's Research & Therapy
Background PSEN1, PSEN2, and APP mutations cause Alzheimer’s disease (AD) with an early age at onset (AAO) and progressive cognitive decline. PSEN1 mutations are more common and generally have an earl...
alzres.biomedcentral.com
January 10, 2025 at 12:47 PM
Integrative multiomics reveals common endotypes across PSEN1, PSEN2, and APP mutations in familial Alzheimer’s disease
alzres.biomedcentral.com/articles/10....
alzres.biomedcentral.com/articles/10....
From @ytquiroz.bsky.social : "In our latest publication, we examined religious stress coping, memory & brain pathology in individuals from the PSEN1 E280A kindred. Religious coping was linked to lower tau and better memory, suggesting a potential protective role worth further study."
Religious stress coping is associated with lower entorhinal tau pathology and better memory performance in autosomal dominant Alzheimer's disease - Jairo E Martinez, Yamile Bocanegra, Ana Baena, Steph...
Stress is a known risk factor for Alzheimer's disease (AD), but religious stress coping practices, (e.g., prayer and attending religious services) may redu...
journals.sagepub.com
April 4, 2025 at 12:21 AM
From @ytquiroz.bsky.social : "In our latest publication, we examined religious stress coping, memory & brain pathology in individuals from the PSEN1 E280A kindred. Religious coping was linked to lower tau and better memory, suggesting a potential protective role worth further study."
It’s time to revisit the narrative around PSEN1—the most common genetic form of Alzheimer’s disease. Contrary to common belief, PSEN1 mutations don’t increase γ-secretase activity or Aβ42. They reduce both.
In this @VJNeurology video, I go over the data:
youtu.be/krc5UGvu7RQ (1/5)
In this @VJNeurology video, I go over the data:
youtu.be/krc5UGvu7RQ (1/5)
From mutation to meaning: revisiting the PSEN1 Alzheimer’s story
YouTube video by VJDementia
youtu.be
April 24, 2025 at 6:28 PM
It’s time to revisit the narrative around PSEN1—the most common genetic form of Alzheimer’s disease. Contrary to common belief, PSEN1 mutations don’t increase γ-secretase activity or Aβ42. They reduce both.
In this @VJNeurology video, I go over the data:
youtu.be/krc5UGvu7RQ (1/5)
In this @VJNeurology video, I go over the data:
youtu.be/krc5UGvu7RQ (1/5)
Plot: Alzheimer's disease (AD) is a late-onset (LO) disease. But 5% of young adults (early-onset/EO) are affected too. Previous studies observed symptoms involving certain mutations from LOAD in EO. Particularly, mutations in PSEN1 form amyloid β plaques, increasing the Aβ42/40 ratio (AD biomarker).
July 4, 2025 at 9:55 AM
Plot: Alzheimer's disease (AD) is a late-onset (LO) disease. But 5% of young adults (early-onset/EO) are affected too. Previous studies observed symptoms involving certain mutations from LOAD in EO. Particularly, mutations in PSEN1 form amyloid β plaques, increasing the Aβ42/40 ratio (AD biomarker).
📃Scientific paper: Location of pathogenic variants in PSEN1 impacts progression of cognitive, clinical, and neurodegene...
➡️ Continued on ES/IODE
➡️ Continued on ES/IODE
July 28, 2024 at 10:18 AM
📃Scientific paper: Location of pathogenic variants in PSEN1 impacts progression of cognitive, clinical, and neurodegene...
➡️ Continued on ES/IODE
➡️ Continued on ES/IODE
CNTN1 interacts with another protein, PSEN1. Higher CNTN1 levels matched higher PSEN1 levels. Increasing PSEN1 reversed the effects of reducing CNTN1, allowing cancer cells to grow and move again.
July 22, 2025 at 10:00 AM
CNTN1 interacts with another protein, PSEN1. Higher CNTN1 levels matched higher PSEN1 levels. Increasing PSEN1 reversed the effects of reducing CNTN1, allowing cancer cells to grow and move again.
[The Wall Street Journal]Three Siblings, One Fatal Gene: A Family’s Fight Against Early-Onset Alzheimer’s - WSJ Among members of the Richardson family who carry a mutation in the PSEN1 gene, the average age when symptoms start is 39
June 30, 2025 at 3:15 PM
[The Wall Street Journal]Three Siblings, One Fatal Gene: A Family’s Fight Against Early-Onset Alzheimer’s - WSJ Among members of the Richardson family who carry a mutation in the PSEN1 gene, the average age when symptoms start is 39
Analysis of whole genome sequence data shows association of Alzheimer's disease with rare coding variants in ABCA7, PSEN1, SORL1 and TREM2 #NeuroDegeneration 🧪🧠
http://medrxiv.org/cgi/content/short/2025.07.27.25332260v1
http://medrxiv.org/cgi/content/short/2025.07.27.25332260v1
July 28, 2025 at 7:01 AM
Analysis of whole genome sequence data shows association of Alzheimer's disease with rare coding variants in ABCA7, PSEN1, SORL1 and TREM2 #NeuroDegeneration 🧪🧠
http://medrxiv.org/cgi/content/short/2025.07.27.25332260v1
http://medrxiv.org/cgi/content/short/2025.07.27.25332260v1
Then treated the samples with SpCas9 enzyme and gRNA. Sequencing the treated samples revealed that the enzyme disrupted the mutant at NGG PAM site in PSEN1 M146L allele, but not the wild type. This indicates the selectivity of SpCas9 enzyme.
July 21, 2025 at 12:38 PM
Then treated the samples with SpCas9 enzyme and gRNA. Sequencing the treated samples revealed that the enzyme disrupted the mutant at NGG PAM site in PSEN1 M146L allele, but not the wild type. This indicates the selectivity of SpCas9 enzyme.
Dr. Quiroz and colleagues have found that, in carriers of the PSEN1 autosomal dominant mutation, lower hippocampal volumes were associated with greater depressive symptoms - suggesting a potential intervention. Could treating depression alter dementia course?
pmc.ncbi.nlm.nih.gov/articles/PMC...
pmc.ncbi.nlm.nih.gov/articles/PMC...
September 19, 2025 at 4:56 PM
Dr. Quiroz and colleagues have found that, in carriers of the PSEN1 autosomal dominant mutation, lower hippocampal volumes were associated with greater depressive symptoms - suggesting a potential intervention. Could treating depression alter dementia course?
pmc.ncbi.nlm.nih.gov/articles/PMC...
pmc.ncbi.nlm.nih.gov/articles/PMC...