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Basic Science and Pathogenesis.

Andrea Trevisiol1, Dustin Loren V Almanza2,3, Margaret M Koletar2

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A high-calorie, high-fat diet partially normalized brain activity in Alzheimer's disease (AD) models by restoring neural power and synchronization. However, this diet may negatively impact normal brain aging.

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Area of Science:

  • Neuroscience
  • Metabolic Research
  • Aging Research

Background:

  • Alzheimer's disease (AD) is linked to impaired brain glucose metabolism, causing neuronal energy deficits and network dysfunction.
  • Obesity is a common comorbidity with AD, prompting investigation into dietary impacts on AD pathology.
  • The study examines how a high-calorie, high-fat (HCHF) diet affects established AD in TgF344-AD rats.

Purpose of the Study:

  • To investigate the effects of a HCHF diet on neuronal function in rats with established Alzheimer's disease (AD) pathology.
  • To evaluate how HCHF diet modulates neuronal activity and network dynamics in the presence and absence of AD-related transgenes.
  • To determine if metabolic interventions can normalize neuronal activity in the context of AD.

Main Methods:

  • TgF344-AD (TgAD) and wild-type (nTg) rats were fed either a standard chow or a HCHF diet for 3 months.
  • Neuronal activity in the somatosensory cortex and hippocampus was recorded using Neuropixels electrodes.
  • Analysis included local field potentials (LFPs) and spiking activity, examining spectral power, phase-amplitude coupling (MI), and spiking rates during rest and forepaw stimulation.

Main Results:

  • Chow-fed TgAD rats showed reduced resting alpha power and attenuated stimulation-induced power increases compared to controls.
  • HCHF feeding restored resting theta and alpha power in TgAD rats and enhanced stimulus-induced power changes.
  • HCHF diet modulated hippocampal theta and gamma synchronization and attenuated spiking responses in the AD hippocampus, but not the cortex.

Conclusions:

  • The HCHF diet demonstrated a partial rescue of AD-related neuronal activity deficits, restoring baseline power and synchronization.
  • These findings suggest the HCHF diet may act as a transient metabolic intervention for normalizing neuronal activity in the AD brain.
  • Conversely, the HCHF diet appears detrimental to neuronal function in normal aging contexts.