Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020;75(1):1-14.
doi: 10.3233/JAD-190848.

Is Alzheimer's Disease a Liver Disease of the Brain?

Affiliations
Review

Is Alzheimer's Disease a Liver Disease of the Brain?

Margaret F Bassendine et al. J Alzheimers Dis. 2020.

Abstract

Clinical specialization is not only a force for progress, but it has also led to the fragmentation of medical knowledge. The focus of research in the field of Alzheimer's disease (AD) is neurobiology, while hepatologists focus on liver diseases and lipid specialists on atherosclerosis. This article on AD focuses on the role of the liver and lipid homeostasis in the development of AD. Amyloid-β (Aβ) deposits accumulate as plaques in the brain of an AD patient long before cognitive decline is evident. Aβ generation is a normal physiological process; the steady-state level of Aβ in the brain is determined by balance between Aβ production and its clearance. We present evidence suggesting that the liver is the origin of brain Aβ deposits and that it is involved in peripheral clearance of circulating Aβ in the blood. Hence the liver could be targeted to decrease Aβ production or increase peripheral clearance.

Keywords: Alzheimer’s disease; apolipoprotein E; circadian; hepatitis C virus; liver; metabolic syndrome; small interfering RNAs.

PubMed Disclaimer

Conflict of interest statement

Authors’ disclosures available online (https://www.j-alz.com/manuscript-disclosures/19-0848r2).

Figures

Fig.1
Fig.1
Some factors altering the balance between amyloid Aβ production and clearance leading to dyshomeostasis. Peripheral clearance can remove 40–50% of Aβ burden in the brain [25, 26]. Aβ, amyloid-β; AβPP, amyloid-β protein precursor, LRP1, low-density lipoprotein receptor-related peptide 1; LDLR, low-density-lipoprotein receptor; P-gp, P-glycoprotein.
Fig.2
Fig.2
Schematic representation of Alzheimer’s disease homeostasis showing amyloid-β (Aβ) production from amyloid-β protein precursor (AβPP) in the liver, dysregulated influx/efflux across blood-brain barrier (BBB) (1), transport in serum via soluble LRP1 (2) and exosomes [61] and saturable uptake of Aβ by liver via low-density lipoprotein receptor-related peptide 1 (LRP1) and low-density-lipoprotein receptor (LDLR) (3) with subsequent biliary clearance. RAGE, receptor for advanced glycation end products.

References

    1. Fitzgerald E, Murphy S, Martinson HA (2019) Alpha-synuclein pathology and the role of the microbiota in Parkinson’s disease. Front Neurosci 13, 369. - PMC - PubMed
    1. Heron M (2016) Deaths: Leading causes for 2014. Natl Vital Stat Rep 65, 1–96. - PubMed
    1. Querfurth HW, LaFerla FM (2010) Alzheimer’s disease. N Engl J Med 362, 329–344. - PubMed
    1. Selkoe DJ, Hardy J (2016) The amyloid hypothesis of Alzheimer’s disease at 25 years. EMBO Mol Med 8, 595–608. - PMC - PubMed
    1. Hardy J (2006) A hundred years of Alzheimer’s disease research. Neuron 52, 3–13. - PubMed

Publication types

Substances