ArticleScience advances2025
Impaired parvalbumin interneurons in the retrosplenial cortex as the cause of sex-dependent vulnerability in Alzheimer's disease.
Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Parvalbumin interneurons in Alzheimer's disease: Physiological insights and pathophysiological mechanisms.Journal of cell communication and signaling · 2026Review
- Integrative transcriptomics identifies shared aging-associated inhibitory-neuron states and prioritizes RGL2 across postoperative delirium and Alzheimer's disease.Journal of molecular neuroscience : MN · 2026Article
- Genetic alterations in SUPT6H are associated with neurodevelopmental disorders.Biochimica et biophysica acta. Molecular basis of disease · 2026Article
- Dual platform spatial transcriptomics reveals parvalbumin interneuron subtype vulnerability in mouse models of Alzheimer's disease.Nature communications · 2026Article
- Reciprocal molecular and cellular cholinergic working memory impairments in Alzheimer's disease model mice.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Braking Parkinson's progression: the hypothetical druggable role of striatal parvalbumin interneurons.NPJ Parkinson's disease · 2026Review
- Sex differences in cerebrovascular function across an aerobic exercise intervention in older adults using MRI: Results from the Brain in Motion study.Physiological reports · 2026Article
- Selective weakening of population-coupled synaptic activity in vivo in a mouse model of amyloid-beta pathology.Nature communications · 2026Article
- Environmental Enrichment Preserves Retrosplenial Parvalbumin Density and Cognitive Function in Female 5xFAD Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Abnormal Neuronal Excitability and Reduced Parvalbumin Expression in Shank3-Deficient Parvalbumin Neurons of the Thalamic Reticular Nucleus.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
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9 authors.
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Abstract
Alzheimer's disease is a debilitating neurodegenerative disorder with no cure and few treatment options. In early stages of Alzheimer's disease, impaired metabolism and functional connectivity of the retrosplenial cortex strongly predict future cognitive impairments. Therefore, understanding Alzheimer's disease-related deficits in the retrosplenial cortex is critical for understanding the origins of cognitive impairment and identifying early treatment targets. Using the 5xFAD mouse model, we discovered early, sex-dependent alterations in parvalbumin-interneuron transcriptomic profiles. This corresponded with impaired parvalbumin-interneuron activity, which was sufficient to induce cognitive impairments and dysregulate retrosplenial functional connectivity. In fMRI scans from patients with mild cognitive impairment and Alzheimer's disease, we observed a similar sex-dependent dysregulation of retrosplenial cortex functional connectivity and, in postmortem tissue from subjects with Alzheimer's disease, a loss of parvalbumin interneurons. Reversal of cognitive deficits by stimulation of parvalbumin interneurons in the retrosplenial cortex suggests that this may serve as a promising therapeutic strategy.
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