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Related Experiment Video

Updated: Jan 8, 2026

Mouse Footpad Inoculation Model to Study Viral-Induced Neuroinflammatory Responses
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Basic Science and Pathogenesis.

Kai Christian Sonntag1, Bruce M Cohen1

  • 1McLean Hospital, Harvard Medical School, Belmont, MA, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 23, 2025
PubMed
Summary
This summary is machine-generated.

Dysfunctional cellular bioenergetics, including reduced nicotinamide adenine dinucleotide (NAD) and glucose metabolism, is an inherent risk factor for late-onset Alzheimer's disease (LOAD). These metabolic deficits may predispose individuals to LOAD neuropathology early in life.

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Area of Science:

  • Neuroscience
  • Cell Biology
  • Metabolic Research

Background:

  • Age is the primary risk factor for late-onset Alzheimer's disease (LOAD).
  • Cellular aging processes overlap with LOAD pathology, with bioenergetic metabolism playing a crucial role.
  • Acquired and genetically determined factors contribute to LOAD, alongside normal aging.

Purpose of the Study:

  • To investigate the role of bioenergetic metabolism in LOAD pathogenesis.
  • To establish a cellular platform for studying LOAD in the context of aging and disease.
  • To identify cell-specific metabolic dysfunctions as potential risk factors for LOAD.

Main Methods:

  • Developed a cellular platform using skin fibroblasts and blood cells from LOAD patients and controls.
  • Utilized induced pluripotent stem cell (iPSC) technology to generate brain cells.
  • Assessed bioenergetic and metabolic cell functions using molecular and biochemical assays.

Main Results:

  • Observed deficiencies in bioenergetic substrates in fibroblasts and iPSC-derived brain cells from LOAD subjects.
  • Found reduced levels of nicotinamide adenine dinucleotide (NAD) and impaired glucose uptake/metabolism.
  • Identified alterations in bioenergetic-dependent cellular functions in LOAD cells.

Conclusions:

  • Dysfunctional bioenergetics is a cell-specific, cell-autonomous risk factor in LOAD.
  • Inherent metabolic dysfunctions may occur early in life, altering aging trajectories and predisposing to LOAD.
  • Further research aims to identify therapeutic targets for early intervention in LOAD.