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

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...

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Bibliographic Details
Published in:Molecular psychiatry Vol. 25; no. 11; pp. 2952 - 2969
Main Authors: Yu, Qianhui, He, Zhisong, Zubkov, Dmitry, Huang, Shuyun, Kurochkin, Ilia, Yang, Xiaode, Halene, Tobias, Willmitzer, Lothar, Giavalisco, Patrick, Akbarian, Schahram, Khaitovich, Philipp
Format: Journal Article
Language:English
Published: England Nature Publishing Group 01.11.2020
Subjects:
Adolescent
Adult
Aged
Aged, 80 and over
Aging
Aging - metabolism
Autism
Child
Child, Preschool
Cognition
Cognitive ability
Cognitive Dysfunction - metabolism
Cortex (temporal)
Down's syndrome
Female
Fluidity
Genetic diversity
Humans
Infant
Lipidomics
Lipids
Male
Membrane fluidity
Mental disorders
Middle Aged
Nonagenarian
Prefrontal cortex
Prefrontal Cortex - growth & development
Prefrontal Cortex - metabolism
Schizophrenia
Substantia grisea
Young Adult
ISSN:1359-4184, 1476-5578, 1476-5578
Online Access:Get full text
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Summary: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.
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ISSN:1359-4184
1476-5578
1476-5578
DOI:10.1038/s41380-018-0200-8