Ketogenic Diet Enhances Cognitive-Behavioral Function and Hippocampal Neurogenesis While Attenuating Amyloid Pathology in Tg-SwDI Mice

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Detalles Bibliográficos
Publicado en:bioRxiv (Feb 24, 2025)
Autor principal: Pulido-Correa, Victoria Eugenia
Otros Autores: Hernandez, Ariana, Wind, Eleanor J, Zhu, Yingying, Vogel, Chana, Shaina Binu, Jeneske, Mikayla, Kuni, Dylan, Chiduruppa, Vedika, Echeverria, Bianca, Rosenberg, Lauren, Robison, Lisa Suzanne
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Cold Spring Harbor Laboratory Press
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Acceso en línea:Citation/Abstract
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022 |a 2692-8205 
024 7 |a 10.1101/2025.02.19.639138  |2 doi 
035 |a 3170647140 
045 0 |b d20250224 
100 1 |a Pulido-Correa, Victoria Eugenia 
245 1 |a Ketogenic Diet Enhances Cognitive-Behavioral Function and Hippocampal Neurogenesis While Attenuating Amyloid Pathology in Tg-SwDI Mice 
260 |b Cold Spring Harbor Laboratory Press  |c Feb 24, 2025 
513 |a Working Paper 
520 3 |a The ketogenic diet (KD), characterized by high-fat, low-carbohydrate, and moderate protein intake, has gained attention for its therapeutic potential in patients with neurodegenerative diseases, including Alzheimer's disease. Studies in Alzheimer's rodent models report that KD and/or ketogenic supplements attenuate cognitive-behavioral impairments, neuroinflammation, amyloid-beta plaques and tau pathology. However, it is unknown whether KD can similarly benefit individuals with cerebral amyloid angiopathy (CAA), a prevalent condition in which amyloid accumulates in cerebral vessels. CAA is highly comorbid in patients with Alzheimer's and, on its own, increases the risk of stroke, cognitive impairment, and dementia, yet no effective treatments currently exist. The objective of this study was to determine whether KD can improve cognitive-behavioral and neuropathological outcomes in a mouse model with CAA. Male Tg-SwDI mice were fed either a standard chow or KD from 3.5 to 7.5 months of age. Following ~3 months of dietary intervention, glucose and ketone-body levels were assessed, then mice underwent a battery of behavioral tests to evaluate locomotor activity, anxiety-related behaviors, and cognition. Immunohistochemistry was performed to assess amyloid pathology, vascular density, neuroinflammation, white matter integrity, and hippocampal neurogenesis. In addition to KD inducing nutritional ketosis and achieving metabolic benefits, mice on KD exhibited increased activity, enhanced spatial learning and memory, and a trend toward improved spatial working memory. These cognitive benefits were accompanied by an attenuation of amyloid pathology and increased hippocampal neurogenesis. These findings suggest that a ketogenic diet may be safe and effective in Alzheimer's and dementia patients with CAA.Competing Interest StatementThe authors have declared no competing interest. 
653 |a Hippocampus 
653 |a Cerebral amyloid angiopathy 
653 |a Memory 
653 |a Low carbohydrate diet 
653 |a Alzheimer's disease 
653 |a Pathology 
653 |a Neurogenesis 
653 |a High fat diet 
653 |a Spatial memory 
653 |a Short term memory 
653 |a Dementia 
653 |a Locomotor activity 
653 |a Dementia disorders 
653 |a Substantia alba 
653 |a Immunohistochemistry 
653 |a Diet 
653 |a Neurodegenerative diseases 
653 |a Animal models 
653 |a Spatial discrimination learning 
653 |a Tau protein 
653 |a Ketogenesis 
700 1 |a Hernandez, Ariana 
700 1 |a Wind, Eleanor J 
700 1 |a Zhu, Yingying 
700 1 |a Vogel, Chana 
700 1 |a Shaina Binu 
700 1 |a Jeneske, Mikayla 
700 1 |a Kuni, Dylan 
700 1 |a Chiduruppa, Vedika 
700 1 |a Echeverria, Bianca 
700 1 |a Rosenberg, Lauren 
700 1 |a Robison, Lisa Suzanne 
773 0 |t bioRxiv  |g (Feb 24, 2025) 
786 0 |d ProQuest  |t Biological Science Database 
856 4 1 |3 Citation/Abstract  |u https://www.proquest.com/docview/3170647140/abstract/embedded/7BTGNMKEMPT1V9Z2?source=fedsrch 
856 4 0 |3 Full Text - PDF  |u https://www.proquest.com/docview/3170647140/fulltextPDF/embedded/7BTGNMKEMPT1V9Z2?source=fedsrch 
856 4 0 |3 Full text outside of ProQuest  |u https://www.biorxiv.org/content/10.1101/2025.02.19.639138v1