Basic Science and Pathogenesis

Area of Science:

• Environmental Health
• Metabolomics
• Neurodegenerative Diseases

Background:

• Serum dichlorodiphenyldichloroethylene (DDE), a metabolite of DDT, is linked to cognitive impairment and Alzheimer's Disease (AD) risk.
• High-resolution metabolomics reveals metabolic phenotypes associated with early cognitive changes and AD.
• Metabolic alterations in midlife serum related to DDE preceding cognitive dysfunction require characterization.

Purpose of the Study:

• To characterize midlife serum metabolome changes associated with dichlorodiphenyldichloroethylene (DDE) exposure.
• To investigate potential metabolic precursors to cognitive dysfunction and AD.

Main Methods:

• Analysis of 362 subjects from the Child Health and Development Studies (CHDS) cohort.
• Cross-sectional analysis of midlife serum p,p'-DDE, metabolome, and exposome using LC-MS and GC-MS.
• Metabolome-wide association study (MWAS) to identify DDE-associated metabolic pathways.

Main Results:

• p,p'-DDE was associated with alterations in fatty acid metabolism pathways (carnitine shuttle, biosynthesis, arachidonic acid, prostaglandin, glycerophospholipid).
• Metabolism of alanine and aspartate amino acids were linked to p,p'-DDE.
• Decreased levels of essential fatty acids (DHA, EPA) and acylcarnitines were observed with increasing serum p,p'-DDE.

Conclusions:

• Midlife DDE-associated metabolic changes overlap with those linked to cognitive dysfunction and AD.
• These findings highlight potential metabolic mediators in cognitive decline and AD onset.
• Relating midlife serum DDE and metabolome may elucidate biological mechanisms in AD.