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Cited by 50Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Targeting Alzheimer’s Disease: The Critical Crosstalk between the Liver and Brain

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Huang, Zhihai, Lin, Hung Wen (Kevin), Zhang, Quanguang, Zong, Xuemei·2022·Nutrients
DOI 10.3390/nu14204298PMC PMC9609624
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Abstract

Alzheimer’s disease (AD), an age-related neurodegenerative disorder, is currently incurable. Imbalanced amyloid-beta (Aβ) generation and clearance are thought to play a pivotal role in the pathogenesis of AD. Historically, strategies targeting Aβ clearance have typically focused on central clearance, but with limited clinical success. Recently, the contribution of peripheral systems, particularly the liver, to Aβ clearance has sparked an increased interest. In addition, AD presents pathological features similar to those of metabolic syndrome, and the critical involvement of brain energy metabolic disturbances in this disease has been recognized. More importantly, the liver may be a key regulator in these abnormalities, far beyond our past understanding. Here, we review recent animal and clinical findings indicating that liver dysfunction represents an early event in AD pathophysiology. We further propose that compromised peripheral Aβ clearance by the liver and aberrant hepatic physiological processes may contribute to AD neurodegeneration. The role of a hepatic synthesis product, fibroblast growth factor 21 (FGF21), in the management of AD is also discussed. A deeper understanding of the communication between the liver and brain may lead to new opportunities for the early diagnosis and treatment of AD.

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  • Researchers have proposed that impaired liver function due to chronic liver diseases and inflammation leads to an imbalance in peripheral Aβ clearance, exacerbating amyloid burden and Alzheimer's pathology.

    “Researchers have proposed that impaired liver function due to chronic liver diseases and inflammation leads to an imbalance in peripheral Aβ clearance, exacerbating amyloid burden and Alzheimer’s pathology [57, 58]”

    From Age, sex and Alzheimer’s disease: a longitudinal study of 3xTg-AD mice reveals sex-specific disease trajectories and inflammatory responses mirrored in postmortem brains from Alzheimer’s patients (2024) · cites this paper as [58]

    Section 4.2 reports that cirrhosis is associated with elevated plasma Aβ and suggests liver dysfunction may reduce peripheral Aβ clearance; the Conclusions say disturbed peripheral Aβ metabolism may contribute to AD progression. But the paper does not establish inflammation as the cause of impaired clearance, and Section 6 says whether liver dysfunction directly exacerbates brain Aβ burden remains unclear. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Huang, Z., Lin, H. W. (., Zhang, Q., & Zong, X.
Affiliations
Louisiana State University (US)
Corresponding author
  • Zhang, Quanguang
  • Zong, Xuemei
ORCID
Venue
Nutrients
Publisher
MDPI AG
Published
2022-10-14
Volume
14
Issue
20
Pages
4298
ISSN
2072-6643 (ISSN-L)
DOI
10.3390/nu14204298
PMC
PMC9609624
OpenAlex
W4306399036
Cited by
50
References
17
Citations by year
2026: 10 · 2025: 13 · 2024: 20 · 2023: 7
FWCI
1.65
Type
journal article
Language
en
Open access
Licence
Locations
  • Nutrients (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Institute of Aging (1RF1AG058603)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
Alzheimer's disease, amyloid-beta clearance, liver-brain axis, liver dysfunction, metabolic syndrome, brain energy metabolism, FGF21, neurodegeneration
MeSH terms
Alzheimer Disease, Animals, Brain, Liver, Amyloid beta-Peptides

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