Cholesterol in Brain Health and Pathologies: The Role in Alzheimer’s Disease
Pp. 26-77 (52)
Kosara Smiljanic, Natasa Loncarevic-Vasiljkovic, Selma Kanazir and Aleksandra Mladenovic Djordjevic
Cholesterol is the molecule essential for life, but also with a possible
detrimental role. Apart from being a vital structural constituent of the cells, cholesterol
is a factor involved in many important cell processes. However, it has been known that
high blood cholesterol is associated with many pathological conditions. An elevated
level of cholesterol is linked with cardiovascular disease, diabetes and
Almost quarter of the total cholesterol in the body resides in the brain. This vast pool is
synthesized in situ and it is almost completely isolated and independent from the
periphery due to the presence of blood-brain barrier. In the central nervous system,
cholesterol plays important role in neural cells structure and functions, including
synaptic transmission. Due to this, its content must be precisely maintained in order to
keep brain function well. However, cholesterol is critically challenged in the aging
brain and disturbed in several of pathological conditions, like Huntington’s disease
(HD), Parkinson’s disease (PD), Niemann-Pick type C (NPC) disease and Smith-Lemli
Opitz syndrome (SLOS), traumatic brain injury, multiple sclerosis (MS) and in
Alzheimer’s disease (AD).
Altered cholesterol metabolism has been extensively implicated in the pathogenesis of
AD. A growing amount of evidence underscores the link between disturbed
intracellular trafficking of cholesterol in the brain and the formation of amyloid
plaques. The inheritance of the epsilon4 allele of the Apolipoprotein E (ApoE), the
main transport protein for cholesterol in the brain represents the main risk factor for
late onset form of Alzheimer’s disease. Other genetic polymorphisms associated with
critical points in cholesterol metabolism may also contribute to the AD pathogenesis.
Hypercholesterolemia has been considered nowadays also as a risk factor, and all of
these players are thought to promote the production of beta-amyloid and development
of AD. Additional proof towards cholesterol involvement in the pathogenesis of AD
gave epidemiological data of the cholesterol-lowering drugs, statins that have been
shown to decrease the risk for AD.
This chapter is aimed to summarize existing knowledge about the brain cholesterol
metabolism, how the homeostasis is changed during aging and in various neurodegenerative
diseases, with special emphasis on Alzheimer’s disease. As a final point,
we will try to give a full insight into the environmental influences (including dietary
restriction and statins therapy) on brain cholesterol homeostasis.
Aging, Alzheimer’s disease, Brain injury, Central nervous system,
Cholesterol homeostasis, Cholesterol metabolism, Dietary restriction,
Neurodegenerative diseases, Oxysterols, Statins.
Institute for Biological Research “Sinisa Stankovic”, University of Belgrade, Belgrade, Serbia