Obesity differentially effects the somatosensory cortex and striatum of TgF344-AD rats

Minhal Ahmed , Aaron Y Lai , Mary E Hill

Biorxiv : the Preprint Server for Biology +

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March 28, 2024

View abstract on PubMed

Summary

Mid-life obesity increases Alzheimer's disease (AD) risk, but late-life obesity may be protective. This study found high-carbohydrate, high-fat diets paradoxically protected against AD progression in specific brain regions.

Area Of Science

Neuroscience
Metabolic Disorders
Aging Research

Background

Mid-life obesity, hypertension, and diabetes are risk factors for late-life Alzheimer's disease (AD).
Paradoxically, obesity in late-life or late-stage AD may reduce AD risk and slow disease progression.
Understanding the mechanisms behind this obesity paradox is crucial for developing effective AD interventions.

Approach

TgF344-AD rats were fed a high-carbohydrate, high-fat (HCHF) diet from 9 to 12 months of age to induce obesity and model AD.
Researchers hypothesized that gray matter regions (e.g., somatosensory cortex) would be affected differently than white matter regions (e.g., striatum).
Brain tissue was analyzed for changes in myelination, oligodendrocytes, neuronal loss, and inflammation.

Key Points

HCHF diet-induced obesity led to increased myelin and oligodendrocytes in the somatosensory cortex (gray matter).
Neuronal loss was absent in the somatosensory cortex, and inflammation decreased despite increased AD pathology.
The striatum (white matter) showed fewer changes compared to the somatosensory cortex.
These findings suggest diet-induced obesity affects myelination in a region-specific manner.

Conclusions

The interaction between diet and AD progression influences myelination differentially across brain regions.
Gray matter regions with lower white matter density appear preferentially affected by diet-related changes.
This study provides a potential mechanistic explanation for the observed obesity paradox in Alzheimer's disease.