Alterations in cholesterol metabolism as a risk factor for developing Alzheimer’s disease: Potential novel targets for treatment

Alzheimer's disease (AD) is the most common form of dementia and it is characterized by the deposition of amyloid-β (Aβ) plaques and neurofibrillary tangles in the brain. However, the complete pathogenesis of the disease is still unknown. High level of serum cholesterol has been found to positi...

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Published inThe Journal of steroid biochemistry and molecular biology Vol. 190; pp. 104 - 114
Main Authors Loera-Valencia, Raúl, Goikolea, Julen, Parrado-Fernandez, Cristina, Merino-Serrais, Paula, Maioli, Silvia
Format Journal Article
LanguageEnglish
Published England Elsevier Ltd 01.06.2019
Elsevier BV
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Abstract Alzheimer's disease (AD) is the most common form of dementia and it is characterized by the deposition of amyloid-β (Aβ) plaques and neurofibrillary tangles in the brain. However, the complete pathogenesis of the disease is still unknown. High level of serum cholesterol has been found to positively correlate with an increased risk of dementia and some studies have reported a decreased prevalence of AD in patients taking cholesterol-lowering drugs. Years of research have shown a strong correlation between blood hypercholesterolemia and AD, however cholesterol is not able to cross the Blood Brain Barrier (BBB) into the brain. Cholesterol lowering therapies have shown mixed results in cognitive performance in AD patients, raising questions of whether brain cholesterol metabolism in the brain should be studied separately from peripheral cholesterol metabolism and what their relationship is. Unlike cholesterol, oxidized cholesterol metabolites known as oxysterols are able to cross the BBB from the circulation into the brain and vice-versa. The main oxysterols present in the circulation are 24S-hydroxycholesterol and 27-hydroxycholesterol. These oxysterols and their catalysing enzymes have been found to be altered in AD brains and there is evidence indicating their influence in the progression of the disease. This review gives a broad perspective on the relationship between hypercholesterolemia and AD, cholesterol lowering therapies for AD patients and the role of oxysterols in pathological and non-pathological conditions. Also, we propose cholesterol metabolites as valuable targets for prevention and alternative AD treatments.
AbstractList Alzheimer's disease (AD) is the most common form of dementia and it is characterized by the deposition of amyloid-β (Aβ) plaques and neurofibrillary tangles in the brain. However, the complete pathogenesis of the disease is still unknown. High level of serum cholesterol has been found to positively correlate with an increased risk of dementia and some studies have reported a decreased prevalence of AD in patients taking cholesterol-lowering drugs. Years of research have shown a strong correlation between blood hypercholesterolemia and AD, however cholesterol is not able to cross the Blood Brain Barrier (BBB) into the brain. Cholesterol lowering therapies have shown mixed results in cognitive performance in AD patients, raising questions of whether brain cholesterol metabolism in the brain should be studied separately from peripheral cholesterol metabolism and what their relationship is. Unlike cholesterol, oxidized cholesterol metabolites known as oxysterols are able to cross the BBB from the circulation into the brain and vice-versa. The main oxysterols present in the circulation are 24S-hydroxycholesterol and 27-hydroxycholesterol. These oxysterols and their catalysing enzymes have been found to be altered in AD brains and there is evidence indicating their influence in the progression of the disease. This review gives a broad perspective on the relationship between hypercholesterolemia and AD, cholesterol lowering therapies for AD patients and the role of oxysterols in pathological and non-pathological conditions. Also, we propose cholesterol metabolites as valuable targets for prevention and alternative AD treatments.
Author Merino-Serrais, Paula
Goikolea, Julen
Parrado-Fernandez, Cristina
Maioli, Silvia
Loera-Valencia, Raúl
Author_xml – sequence: 1
  givenname: Raúl
  orcidid: 0000-0001-9376-0049
  surname: Loera-Valencia
  fullname: Loera-Valencia, Raúl
  email: raul.loera@ki.se
  organization: Karolinska Institutet, Center for Alzheimer Research, Department of Neurobiology Care Sciences and Society, Division of Neurogeriatrics, Stockholm, Sweden
– sequence: 2
  givenname: Julen
  surname: Goikolea
  fullname: Goikolea, Julen
  organization: Karolinska Institutet, Center for Alzheimer Research, Department of Neurobiology Care Sciences and Society, Division of Neurogeriatrics, Stockholm, Sweden
– sequence: 3
  givenname: Cristina
  surname: Parrado-Fernandez
  fullname: Parrado-Fernandez, Cristina
  organization: Karolinska Institutet, Center for Alzheimer Research, Department of Neurobiology Care Sciences and Society, Division of Neurogeriatrics, Stockholm, Sweden
– sequence: 4
  givenname: Paula
  surname: Merino-Serrais
  fullname: Merino-Serrais, Paula
  organization: Karolinska Institutet, Center for Alzheimer Research, Department of Neurobiology Care Sciences and Society, Division of Neurogeriatrics, Stockholm, Sweden
– sequence: 5
  givenname: Silvia
  surname: Maioli
  fullname: Maioli, Silvia
  email: silvia.maioli@ki.se
  organization: Karolinska Institutet, Center for Alzheimer Research, Department of Neurobiology Care Sciences and Society, Division of Neurogeriatrics, Stockholm, Sweden
BackLink https://www.ncbi.nlm.nih.gov/pubmed/30878503$$D View this record in MEDLINE/PubMed
http://kipublications.ki.se/Default.aspx?queryparsed=id:141160876$$DView record from Swedish Publication Index
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AMRAJ
ASPBG
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AXJTR
AZFZN
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BLXMC
CS3
DOVZS
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LX3
M41
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O-L
O9-
OAUVE
OZT
P-8
P-9
P2P
PC.
Q38
R2-
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ROL
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SBG
SDF
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AAXKI
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FR3
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P64
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7X8
ADTPV
AOWAS
D8T
ZZAVC
ABWVN
ID FETCH-LOGICAL-c586t-6ba806b81eb523190fe24074ba2332b75d10607c9fdd5624249ee03c1ca40a693
IEDL.DBID AIKHN
ISSN 0960-0760
1879-1220
IngestDate Tue Dec 17 03:31:59 EST 2024
Wed Oct 30 04:57:55 EDT 2024
Fri Oct 25 12:30:29 EDT 2024
Thu Oct 10 20:22:15 EDT 2024
Fri Dec 06 04:57:59 EST 2024
Wed Oct 16 00:51:37 EDT 2024
Fri Feb 23 02:26:57 EST 2024
IsDoiOpenAccess true
IsOpenAccess true
IsPeerReviewed true
IsScholarly true
Keywords Liver X activated receptor
Alzheimer’s disease
Cytochrome P-450
Cerebral cholesterol
Cholesterol 24S-hydroxylase
Apolipoprotein
Astrocyte
RXR
Efavirenz
Lipid
Amyloid beta
PSD95
Neurodegeneration
Oxysterols
27-Hydroxycholesterol
ACE inhibitors
Statins
Dementia
Language English
License This is an open access article under the CC BY license.
Copyright © 2019. Published by Elsevier Ltd.
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MergedId FETCHMERGED-LOGICAL-c586t-6ba806b81eb523190fe24074ba2332b75d10607c9fdd5624249ee03c1ca40a693
Notes ObjectType-Article-2
SourceType-Scholarly Journals-1
ObjectType-Feature-3
content type line 23
ObjectType-Review-1
ORCID 0000-0001-9376-0049
OpenAccessLink https://www.sciencedirect.com/science/article/pii/S0960076018307702
PMID 30878503
PQID 2233946573
PQPubID 2045443
PageCount 11
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proquest_miscellaneous_2193605010
proquest_journals_2233946573
crossref_primary_10_1016_j_jsbmb_2019_03_003
pubmed_primary_30878503
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PublicationCentury 2000
PublicationDate 2019-06-01
PublicationDateYYYYMMDD 2019-06-01
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  year: 2019
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  day: 01
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PublicationTitle The Journal of steroid biochemistry and molecular biology
PublicationTitleAlternate J Steroid Biochem Mol Biol
PublicationYear 2019
Publisher Elsevier Ltd
Elsevier BV
Publisher_xml – name: Elsevier Ltd
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Snippet Alzheimer's disease (AD) is the most common form of dementia and it is characterized by the deposition of amyloid-β (Aβ) plaques and neurofibrillary tangles in...
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SubjectTerms 27-Hydroxycholesterol
ACE inhibitors
Alzheimer's disease
Amyloid
Amyloid beta
Apolipoprotein
Astrocyte
Blood-brain barrier
Brain
Cerebral cholesterol
Cholesterol
Cholesterol 24S-hydroxylase
Cognitive ability
Cytochrome P-450
Dementia
Dementia disorders
Efavirenz
Hypercholesterolemia
Lipid
Lipid metabolism
Liver X activated receptor
Medicin och hälsovetenskap
Metabolism
Metabolites
Neurodegeneration
Neurodegenerative diseases
Neurofibrillary tangles
Oxysterols
PSD95
RXR
Senile plaques
Statins
Title Alterations in cholesterol metabolism as a risk factor for developing Alzheimer’s disease: Potential novel targets for treatment
URI https://dx.doi.org/10.1016/j.jsbmb.2019.03.003
https://www.ncbi.nlm.nih.gov/pubmed/30878503
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