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Cited by 144Alzheimer's disease research and treatmentsBarrier Structure and Function StudiesDementia and Cognitive Impairment Research

Liver Dysfunction as a Novel Player in Alzheimer’s Progression: Looking Outside the Brain

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Estrada, Lisbell D., Ahumada, Pablo, Cabrera, Daniel, Arab, Juan P.·2019·Frontiers in Aging Neuroscience
DOI 10.3389/fnagi.2019.00174PMC PMC6650779
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Abstract

Alzheimer's disease (AD) afflicts an estimated 20 million people worldwide and is the fourth-leading cause of death in the developed world. The most common cause of dementia in older individuals, AD is characterized by neuropathologies including synaptic and neuronal degeneration, amyloid plaques, and neurofibrillary tangles (NTFs). Amyloid plaques are primarily composed of amyloid-beta peptide (Aβ), which accumulates in the brains of patients with AD. Further, small aggregates termed Aβ oligomers are implicated in the synaptic loss and neuronal degeneration underlying early cognitive impairments. Whether Aβ accumulates in part because of dysregulated clearance from the brain remains unclear. The flow of substances (e.g., nutrients, drugs, toxins) in and out of the brain is mediated by the blood-brain-barrier (BBB). The BBB exhibits impairment in AD patients and animal models. The effect of BBB impairment on Aβ, and whether BBB function is affected by non-neurological pathologies that impair peripheral clearance requires further investigation. In particular, impaired peripheral clearance is a feature of nonalcoholic fatty liver disease (NAFLD), a spectrum of liver disorders characterized by accumulation of fat in the liver accompanied by varying degrees of inflammation and hepatocyte injury. NAFLD has reached epidemic proportions, with an estimated prevalence between 20% and 30% of the general population. This chronic condition may influence AD pathogenesis. This review article summarizes the current state of the literature linking NAFLD and AD, highlighting the role of the major Aβ efflux and clearance protein, the LRP-1 receptor, which is abundantly expressed in liver, brain, and vasculature.

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Cited by

Sorted by citations

Authors
Estrada, L. D., Ahumada, P., Cabrera, D., & Arab, J. P.
Affiliations
  • Universidad Bernardo O'Higgins (CL)
  • Pontificia Universidad Católica de Chile (CL)
Corresponding author
Estrada, Lisbell D.
ORCID
Venue
Frontiers in Aging Neuroscience
Publisher
Frontiers Media SA
Published
2019-07-17
Volume
11
Pages
174-174
ISSN
1663-4365 (ISSN-L)
DOI
10.3389/fnagi.2019.00174
PMC
PMC6650779
OpenAlex
W2959600071
Cited by
144
References
14
Citations by year
2026: 14 · 2025: 18 · 2024: 30 · 2023: 19 · 2022: 28 · 2021: 20 · 2020: 15
FWCI
10.55
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Aging Neuroscience (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Fondo Nacional de Desarrollo Científico y Tecnológico
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
Alzheimer's disease, non-alcoholic fatty liver disease, amyloid-beta, amyloid-beta oligomers, blood-brain barrier, amyloid-beta clearance, liver dysfunction, neurodegeneration, amyloid plaques, neurofibrillary tangles

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