Researchers from the IIS La Fe and INCLIVA conduct a review on lipid alteration in brain tissue and blood to identify biomarkers for early detection of Alzheimer's disease.

Changes in lipid composition observed so far in both human brain and transgenic mouse models are associated with neurodegenerative disorders.

50 million people currently suffer from dementia, mostly attributed to AD, and the number is expected to rise to 139 million by 2050 if effective therapies are not introduced.

Researchers from the INCLIVA Health Research Institute and the La Fe Health Research Institute (IIS La Fe) in Valencia have carried out a review of lipid alteration in brain tissue and blood of animal mouse models of Alzheimer's disease (AD), with the ultimate aim of helping to identify lipid biomarkers in blood samples that could be useful in the early and minimally invasive detection of this pathology.

The work, which has just been published in Progress in Lipid Research, involved Dr Ana Lloret, a researcher from the INCLIVA Research Group on Ageing and Physical Exercise, CIBERFES (Centre for Biomedical Research Network on Fragility and Healthy Ageing) of the Carlos III Health Institute and the Department of Physiology of the Faculty of Medicine of the University of Valencia; and Consuelo Cháfer Pericás and Laura Ferré González, from the Alzheimer's Disease Research Group of the IIS La Fe.

The aim of this work was to make a systematic review of the studies conducted from 2012 to the present on lipid alteration in brain tissue and blood of mouse animal models with AD, focusing on the different experimental parameters evaluated in these studies (type of sample, sex, mouse model, age, sample treatment and analytical technique used), since the changes in lipid composition that have been observed so far in both human brain and transgenic mouse models are associated with neurodegenerative disorders.

Approximately 50 million people suffer from dementia worldwide and the majority of cases are attributed to AD. If effective therapies are not introduced, the global prevalence of AD is expected to increase to 139 million by 2050. Currently, the diagnosis of AD is based on invasive and expensive techniques. Therefore, it would be an advantage to find biomarkers in minimally invasive samples and using cost-effective methods. Among the different biomarkers, lipids could play an important role, as they are the main component of the brain and are involved in the function and structure of neuronal membranes.

Symptoms of AD include memory impairment, aphasia (a language disorder that makes it difficult to read, write and express what is meant) and visuospatial deficits.

Animal models have been widely used to understand the mechanisms underlying many diseases, to explore the efficacy of drug candidates and to predict patient responses. In the last two decades, several types of transgenic mouse models have been developed that recapitulate the neuropathological and/or behavioural abnormalities of AD.

At present, there is a large variability between studies that have been carried out in mice for the determination of different types of lipids. Therefore, this disparity may be due to the mouse model used, age and sex, but, above all, to some important experimental variables in the pre-treatment and treatment of the sample.

The design of the present systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) method. The electronic data search was performed on 21 June 2022 in the PubMed and Web of Science (WOS) databases and was complemented by a manual search in Google Scholar. The following characteristics were taken into account: sample type (brain tissue or plasma), sex, sample description (AD mouse model and sample size), age (in months), sample treatment and analytical technique.

All information extracted from the articles was pooled, filled in and repeatedly checked for inconsistencies and data accuracy using Microsoft Office Excel.

The review shows that the lipidomic studies carried out since 2012 to date present a wide variety of experimental conditions, which makes it difficult to draw conclusions. In particular, it must be taken into account that, when performing this type of study, there is a great variability of mouse models of AD, and each model has its advantages and disadvantages. Therefore, further research into the pathobiology of AD will allow more accurate mouse models to be established. In addition, the studies did not focus on sex differences, so further research is needed. As for age, the lipidomic profile might change throughout the disease progression and the stage of the disease at which the experiments are performed should be taken into account. In terms of sample pre-treatment, the method of homogenisation seems to be influenced, with mechanical homogenisation being the most reliable in terms of sample uniformity and standardisation. As for the lipid extraction method, there is an urgent need to replace highly toxic solvents such as chloroform and to find environmentally friendly alternatives. Finally, methods using mass spectrometry for lipid detection and quantification provide more information compared to colorimetric kits.

DOI of the article: 10.1016/j.plipres.2023.101223