Beyond cardiovascular risk: Implications of Familial hypercholesterolemia on cognition and brain function

Jade de Oliveira; Eduardo Luiz Gasnhar Moreira; Andreza Fabro de Bem

doi:10.1016/j.arr.2023.102149

Beyond cardiovascular risk: Implications of Familial hypercholesterolemia on cognition and brain function

Ageing Res Rev. 2024 Jan:93:102149. doi: 10.1016/j.arr.2023.102149. Epub 2023 Dec 4.

Authors

Jade de Oliveira¹, Eduardo Luiz Gasnhar Moreira², Andreza Fabro de Bem³

Affiliations

¹ Laboratory of investigation on metabolic disorders and neurodegenerative diseases, Department of Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, RS 90035-003, Brazil. Electronic address: deoliveirajade10@gmail.com.
² Neuroscience Coworking Lab, Department of Physiological Sciences, Federal University of Santa Catarina, Florianópolis, SC 88040-900, Brazil. Electronic address: eduardo.luiz@ufsc.br.
³ Laboratory of Bioenergetics and Metabolism, Department of Physiological Sciences, University of Brasilia, Brasília, Federal District, DF 70910-900, Brazil; Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden; Brazilian National Institute of Science and Technology on Neuroimmunomodulation, Oswaldo Cruz Foundation, Rio de Janeiro, RJ 21040360, Brazil. Electronic address: debemandreza@gmail.com.

PMID: 38056504
DOI: 10.1016/j.arr.2023.102149

Abstract

Familial hypercholesterolemia (FH) is a metabolic condition caused mainly by a mutation in the low-density lipoprotein (LDL) receptor gene (LDLR), which is highly prevalent in the population. Besides being an important causative factor of cardiovascular diseases, FH has been considered an early risk factor for Alzheimer's disease. Cognitive and emotional behavioral impairments in LDL receptor knockout (LDLr^-/-) mice are associated with neuroinflammation, blood-brain barrier dysfunction, impaired neurogenesis, brain oxidative stress, and mitochondrial dysfunction. Notably, today, LDLr^-/- mice, a widely used animal model for studying cardiovascular diseases and atherosclerosis, are also considered an interesting tool for studying dementia. Here, we reviewed the main findings in LDLr^-/- mice regarding the relationship between FH and brain dysfunctions and dementia development.

Keywords: Blood-brain barrier, Neuroinflammation, LDL receptor, LDLr(-/-) mice; Cholesterol; Memory.

Publication types

Review

MeSH terms

Alzheimer Disease*
Animals
Brain / metabolism
Cardiovascular Diseases* / genetics
Cognition
Heart Disease Risk Factors
Humans
Hypercholesterolemia* / epidemiology
Hypercholesterolemia* / genetics
Hypercholesterolemia* / metabolism
Hyperlipoproteinemia Type II* / complications
Hyperlipoproteinemia Type II* / genetics
Mice
Risk Factors