BOSTON — While many clinical studies have reported brain lipidomic abnormalities in Alzheimer’s disease (AD) that affect glycerophospholipids, sphingolipids and fatty acids, no consensus exists about those abnormalities and whether they relate to disease progression.
A study1 led by Boston University Chobanian & Avedisian School of Medicine and including participation from the Boston and Bedford, MA, VAMCs sought to measure the levels of monogalactosyl diglycerides (MGDGs) class of lipids, which have been recently detected in the human brain, in postmortem subjects, and determine whether these levels correlate with the progression of the AD-related traits.
MGDGs were measured by ultrahigh performance liquid chromatography tandem mass spectrometry in postmortem dorsolateral prefrontal cortex gray matter and subcortical corona radiata white matter samples derived from three cohorts, including 288 participants from the Framingham Heart Study, the Boston University Alzheimer’s Disease Research Center and the Arizona Study of Aging and Neurodegenerative Disorders/Brain and Body Donation Program.
The researchers reported in the Journal of Alzheimer’s Disease that they had detected 40 molecular species of MGDGs (including diacyl and alkyl/acyl compounds). They also said they found that the levels of 29 of them, as well as total MGDG levels, are positively associated with AD-related traits including:
- pathologically confirmed AD diagnosis,
- clinical dementia rating,
- Braak and Braak stage,
- neuritic plaque score,
- phospho-Tau AT8 immunostaining density,
- levels of phospho-Tau396 and
- levels of Aβ40.
“Increased MGDG levels were present in both gray and white matter, indicating that they are widespread and likely associated with myelin-producing oligodendrocytes-the principal cell type of white matter,” the authors wrote.
The researchers concluded that their data implicate the MGDG metabolic defect as a central correlate of clinical and pathological progression in AD.
- Blusztajn JK, Aytan N, Rajendiran T, Mellott TJ, Soni T, Burant CF, Serrano GE, Beach TG, Lin H, Stein TD. Cerebral Gray and White Matter Monogalactosyl Diglyceride Levels Rise with the Progression of Alzheimer’s Disease. J Alzheimers Dis. 2023 Sep 14. doi: 10.3233/JAD-230543. Epub ahead of print. PMID: 37718815.
