ArticleNeuron2015
Presenilin-1 knockin mice reveal loss-of-function mechanism for familial Alzheimer's disease.
Article in Neuron, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 158 papers.
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Who cites it
158 citing papers in PubMed, 233 citations in OpenAlex.
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- A Skull Bone Marrow-to-Brain Axis Links Osteoblastic Activity to Myeloid Cell Trafficking, Cerebral Blood Flow, and Cognition in Alzheimer's Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Kat5 cKO mouse replicates biological domain signatures associated with Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- A Humanized Knock-in Mouse Model of the PSEN1 V97L Mutation from a Major Chinese Alzheimer's Disease Pedigree Reveals Early Neuroinflammation.Neuroscience bulletin · 2026Article
- Sound-evoked auditory neurophysiological signals are a window into prodromal functional differences in a preclinical model of Alzheimer's disease.Scientific reports · 2026Article
- Lysosomal homeostasis at the crossroads of neurodegeneration.The Journal of clinical investigation · 2026Review
- Presenilin-dependent regulation of neuronal tau pathology via the autophagy and proteasome pathways.Acta neuropathologica communications · 2026Article
- Cognitive dysfunction in patients with interstitial lung disease.Frontiers in medicine · 2026Article
- A unique subpopulation of wild-type neurons recapitulating familial Alzheimer's disease phenotypes.Cell death & disease · 2025Article
- Identification of presenilin mutations that have sufficient gamma-secretase proteolytic activity to mediate Notch signaling but disrupt organelle and neuronal health.Neurobiology of disease · 2025Article
- Genetic Correlates of Presenile Dementia and Cognitive Decline in the Armenian Population Following COVID-19: A Case-Control Study.International journal of molecular sciences · 2025Article
- PF-06447475 Molecule Attenuates the Neuropathology of Familial Alzheimer's and Coexistent Parkinson's Disease Markers in PSEN1 I416T Dopaminergic-like Neurons.Molecules (Basel, Switzerland) · 2025Article
- Combination of Epigallocatechin-3-Gallate and Tramiprosate Prevent Accumulation of Intracellular Aβ and Dysfunctional Autophagy-Lysosomal Pathway at Earliest Stage of Transdifferentiation of Mesenchymal Stromal Cells into PSEN1 E280A Cholinergic-like Neurons.International journal of molecular sciences · 2025Article
- CRISPR/Cas9-Based therapeutics as a promising strategy for management of Alzheimer's disease: progress and prospects.Frontiers in cellular neuroscience · 2025Review
- Pathophysiologic abnormalities in transgenic mice carrying the Alzheimer disease PSEN1 Δ440 mutation.Human molecular genetics · 2024Article
- Haploinsufficiency and Alzheimer's Disease: The Possible Pathogenic and Protective Genetic Factors.International journal of molecular sciences · 2024Review
- Cortical neurodegeneration caused byProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Presenilin Deficiency Results in Cellular Cholesterol Accumulation by Impairment of Protein Glycosylation and NPC1 Function.International journal of molecular sciences · 2024Article
- Early molecular events of autosomal-dominant Alzheimer's disease in marmosets with PSEN1 mutations.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
98 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Presenilins play essential roles in memory formation, synaptic function, and neuronal survival. Mutations in the Presenilin-1 (PSEN1) gene are the major cause of familial Alzheimer's disease (FAD). How PSEN1 mutations cause FAD is unclear, and pathogenic mechanisms based on gain or loss of function have been proposed. Here, we generated Psen1 knockin (KI) mice carrying the FAD mutation L435F or C410Y. Remarkably, KI mice homozygous for either mutation recapitulate the phenotypes of Psen1(-/-) mice. Neither mutation altered Psen1 mRNA expression, but both abolished γ-secretase activity. Heterozygosity for the KI mutation decreased production of Aβ40 and Aβ42, increased the Aβ42/Aβ40 ratio, and exacerbated Aβ deposition. Furthermore, the L435F mutation impairs hippocampal synaptic plasticity and memory and causes age-dependent neurodegeneration in the aging cerebral cortex. Collectively, our findings reveal that FAD mutations can cause complete loss of Presenilin-1 function in vivo, suggesting that clinical PSEN mutations produce FAD through a loss-of-function mechanism.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.