Alzheimer's

Alzheimer's

This video contains key highlights of latest research results, including those of YouthBio, investigating therapeutic benefits of partial reprogramming of the brain in animal models of Alzheimer’s, memory loss, cognitive decline, adult neurogenesis etc.

Key Scientific Publications

Partial Reprogramming vs. Alzheimer's:

Cognitive rejuvenation through partial reprogramming of engram cells (Berdugo-Vega et al. 2026). Demonstrated that Yamanaka factors gene therapy in engram neurons reverse disease-related hallmarks and restore learning/memory in aged mice and two AD models (5xFAD and APP/PS1):

“partial reprogramming of engram neurons-bona fide memory trace cells-by OSK-mediated gene therapy reversed the expression of senescence- and disease-related cellular hallmarks in aged mice and models of Alzheimer's disease (AD), re-established aberrant epigenetic-transcriptional patterns pertaining to synaptic plasticity, and counteracted AD-typical neuronal hyperexcitability. Importantly, irrespective of the brain area targeted or the behavioral paradigm employed, engram reprogramming also recovered learning and memory capacities to levels of healthy young animals, suggesting cognitive rejuvenation. These results posit that partial reprogramming of specific cell populations in the brain can be exploited for cognitive restoration in aging and disease.”

Partial reprogramming by cyclical overexpression of Yamanaka factors improves pathological phenotypes of tauopathy mouse model of human Alzheimer's disease (Antón-Fernández et al. 2025). Demonstrated that partial reprogramming improves pathological phenotypes in the P301S tauopathy mouse model of AD:

“results of this study show a significant improvement in key pathological features of tauopathies in the hippocampus, including reversed tauopathy, alleviated reactive astrogliosis, age-related reduction of the H3K9me3 epigenetic marker, along with improved spatial memory, which has been described as deteriorated in this model. These findings reinforce the potential of partial reprogramming as a therapeutic strategy to combat brain pathologies associated with aging.”

Expansion of the neocortex and protection from neurodegeneration by in vivo transient reprogramming (Shen et al. 2024). Demonstrated that partial reprogramming with Yamanaka factors can prevent Alzheimer's symptoms in a 5xFAD mouse model of Alzheimer's disease:

“controlled [Yamanaka factors] induction … prevented the development of several hallmarks of Alzheimer’s disease, including cognitive decline and altered molecular signatures, in the 5xFAD mouse model [of Alzheimer’s Disease]”

CRISPR/dCas9-Dnmt3a-mediated targeted DNA methylation of APP rescues brain pathology in a mouse model of Alzheimer’s disease (Park et al. 2022). Demonstrated that Alzheimer's symptoms can be epigenetically prevented:

“Furthermore, the in vivo methylation of APP in the brain via dCas9-Dnmt3a treatment altered Aβ plaques and attenuated cognitive and behavioral impairments in the APP-KI mouse model”

An integrated multi-omics approach identifies epigenetic alterations associated with Alzheimer’s disease (Nativio et al. 2020). Demonstrated epigenetic drivers of Alzheimer's disease:

“These findings suggest that Alzheimer's Disease involves a reconfiguration of the epigenomic landscape, with the marks H3K27ac and H3K9ac affecting disease pathways by disrupting transcription- and chromatin-gene feedback loops. The identification of this process highlights potential strategies to modulate these marks for early-stage disease treatment.”

Inhibition of EHMT1/2 rescues synaptic and cognitive functions for Alzheimer’s disease (Zheng et al. 2019). Demonstrated that Alzheimer's symptoms can be epigenetically reversed:

Other Brain Partial Reprogramming Results:

Restoration of neuronal progenitors by partial reprogramming in the aged neurogenic niche (Xu et al. 2024). Demonstrated that partial reprogramming can induce the creation of novel neurons in the brains of old mice:

“Importantly, partial reprogramming improves the production of new neurons in vitro and in old brains. Our work suggests that partial reprogramming could be used to rejuvenate the neurogenic niche and counter brain decline in old individuals.”

Cognitive rejuvenation in old rats by hippocampal OSKM gene therapy (Horvath et al. 2024). Demonstrated that brain-targeted Yamanaka factors gene therapy can produce cognitive benefits in old rats:

“In summary, the administration of Yamanaka genes via viral vectors rejuvenates the functional capabilities and the epigenetic landscape of the rat hippocampus.”

In Vivo Reprogramming Ameliorates Aging Features in Dentate Gyrus Cells and Improves Memory in Mice (Rodríguez-Matellán et al. 2020). Demonstrated that partial reprogramming can improve memory:

“We conclude that transient cyclic reprogramming in vivo in the central nervous system could be an effective strategy to ameliorate aging of the central nervous system and neurodegenerative diseases”

Regenerative Gene Therapy In The Hypothalamus Prolongs Fertility In Female Rats (Gallardo et al. 2023). Demonstrated that hypothalamus-targeted Yamanaka factors gene therapy can prolong fertility in female rats:

“The particular significance of the present results is that, for the first time, they show that long-term OSKM gene therapy in the hypothalamus is able to extend the functionality of such a complex system as the hypothalamo-pituitary-ovarian axis.”