Lipidome alterations in human prefrontal cortex during development, aging, and cognitive disorders

Qianhui Yu,Tobias Halene,Dmitry Zubkov,Ilia Kurochkin,Schahram Akbarian,Lothar Willmitzer,Zhisong He,Philipp Khaitovich,Xiaode Yang,Shuyun Huang,Patrick Giavalisco

doi:10.1038/s41380-018-0200-8

Abstract

Lipids are essential to brain functions, yet they remain largely unexplored. Here we investigated the lipidome composition of prefrontal cortex gray matter in 396 cognitively healthy individuals with ages spanning 100 years, as well as 67 adult individuals diagnosed with autism (ASD), schizophrenia (SZ), and Down syndrome (DS). Of the 5024 detected lipids, 95% showed significant age-dependent concentration differences clustering into four temporal stages, and resulting in a gradual increase in membrane fluidity in individuals ranging from newborn to nonagenarian. Aging affects 14% of the brain lipidome with late-life changes starting predominantly at 50–55 years of age—a period of general metabolic transition. All three diseases alter the brain lipidome composition, leading—among other things—to a concentration decrease in glycerophospholipid metabolism and endocannabinoid signaling pathways. Lipid concentration decreases in SZ were further linked to genetic variants associated with disease, indicating the relevance of the lipidome changes to disease progression.

Highlights

Lipids take up over half of the brain’s dry weight and are known to play important roles as the brain’s main structural components, as well as energy and signaling molecules [1, 2]
Concentration changes along the lifespan detected in our study correlate significantly with expressions of genes interacting with the lipids (Figure S3)
Our results indicate that four lipidome lifespan stages are conserved among primates and characterized by differential enrichment in specific lipid classes and pathways, suggesting their relevance to functional changes in prefrontal cortex (PFC) organization

Summary

Introduction

Lipids take up over half of the brain’s dry weight and are known to play important roles as the brain’s main structural components, as well as energy and signaling molecules [1, 2]. While brain organization and function experience drastic. These authors contributed : Qianhui Yu, Zhisong He, Dmitry Zubkov. We investigated lipid concentration levels in the gray matter of the dorsolateral prefrontal cortex (PFC) in 396 cognitively healthy humans with ages spanning 100 years of the human lifespan. We compared age-dependent lipidome changes with the lipidome alterations in disorders that commonly affect cognition, by measuring lipid concentrations in PFC samples of SZ, ASD, and DS patients. Based on the concentration levels of more than 5000 hydrophobic compounds (lipids), we were able to characterize the main features of the lipidome changes across the lifespan with unprecedented temporal resolution, assess the extent of metabolic breakdown in aging and gain insights into the role of lipidome alterations in the three common cognitive disorders

Methods

Findings

Discussion

Conclusion