Hippocampal and hypothalamic cell-type specific mechanisms underlying nutritional and metabolic modulation of Alzheimer’s disease
Abstract
To understand the potential of modulating metabolism for therapeutic development for Alzheimer’s disease (AD), we investigated the effects of high fructose consumption as a potential risk, and docosahexaenoic acid (DHA) and nicotinamide riboside (NR) as potentially beneficial, on cell type-specific transcriptomic responses in the hippocampus and hypothalamus of the 5xFAD mouse model. Fructose increased the expression of C3, encoding complement component 3, in ependymal cells and inflammatory genes in microglia, which were normalized by DHA and NR. NR and DHA reversed Aβ-associated transcriptional signatures across cell types, but the effects were modified by fructose. DHA and NR treatments reversed the AD-associated decrease in hippocampal oligodendrocytes, with DHA further reducing hippocampal microglia and increasing hypothalamic astrocytes, and NR further increasing hippocampal neuronal proportions. Our study supports the impact of metabolic regulation of AD-associated cell types and pathways and provides molecular support for utilizing nutritional modulators for AD intervention.
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BibTeX
@article{ding2026hippocampal,
title = {{Hippocampal and hypothalamic cell-type specific mechanisms underlying nutritional and metabolic modulation of Alzheimer’s disease}},
author = {Jessica A. Ding and David Samvelian and Zhe Ying and Graciel Diamante and In Sook Ahn and Victoria Palafox-Sanchez and Susanna Sue-Ming Wang and Fernando Gomez-Pinilla and Xia Yang},
journal = {iScience},
year = {2026},
month = oct,
doi = {10.1016/j.isci.2026.117920},
url = {https://www.cell.com/iscience/fulltext/S2589-0042(26)03303-1},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Hippocampal and hypothalamic cell-type specific mechanisms underlying nutritional and metabolic modulation of Alzheimer’s disease
AU - Jessica A. Ding
AU - David Samvelian
AU - Zhe Ying
AU - Graciel Diamante
AU - In Sook Ahn
AU - Victoria Palafox-Sanchez
AU - Susanna Sue-Ming Wang
AU - Fernando Gomez-Pinilla
AU - Xia Yang
PY - 2026
DA - 2026/10/19
JO - iScience
DO - 10.1016/j.isci.2026.117920
UR - https://www.cell.com/iscience/fulltext/S2589-0042(26)03303-1
AB - To understand the potential of modulating metabolism for therapeutic development for Alzheimer’s disease (AD), we investigated the effects of high fructose consumption as a potential risk, and docosahexaenoic acid (DHA) and nicotinamide riboside (NR) as potentially beneficial, on cell type-specific transcriptomic responses in the hippocampus and hypothalamus of the 5xFAD mouse model. Fructose increased the expression of C3, encoding complement component 3, in ependymal cells and inflammatory genes in microglia, which were normalized by DHA and NR. NR and DHA reversed Aβ-associated transcriptional signatures across cell types, but the effects were modified by fructose. DHA and NR treatments reversed the AD-associated decrease in hippocampal oligodendrocytes, with DHA further reducing hippocampal microglia and increasing hypothalamic astrocytes, and NR further increasing hippocampal neuronal proportions. Our study supports the impact of metabolic regulation of AD-associated cell types and pathways and provides molecular support for utilizing nutritional modulators for AD intervention.
SN - 2589-0042
ER -