Huntington Medical Research Institutes’ (HMRI) neurosciences research team led by senior researcher Alfred N. Fonteh had their original research on the impact of deteriorating membrane lipids in Alzheimer’s disease (AD) published in Frontiers in Neuroscience. Incomplete knowledge of brain lipid composition limits mechanistic insight into late-onset AD pathophysiology. Since age is the most significant risk factor of AD, the HMRI team propose that older neuronal cells render the amyloid precursor protein more vulnerable to abnormal processing because of deteriorating membrane lipids. We compared the lipid composition of cognitively healthy (CH) participants with normal Aß42/Tau (CH-NAT), CH with pathological Aß42/Tau (CH-PAT), and AD. We found differential metabolism of lipids in the supernatant fluid and nanoparticulate membrane fractions of cerebrospinal fluid (CSF). Whereas phosphatidylcholine accumulates in the supernatant fluid fraction, sphingomyelin accumulates in the CH-PAT group’s nanoparticulate membrane fraction. Phospholipase A2 activity that hydrolyzes lipids is higher in AD than in the cognitively healthy groups. Sphingomyelinase activities that hydrolyze sphingomyelin are lower in AD compared to the healthy groups. Similar fasting blood and dietary lipid levels in the three clinical groups are consistent with the CSF lipid changes originating from brain pathophysiology. Our results identify increased lipid turnover in cognitively healthy participants with AD biomarkers, switching to a predominantly lipolytic state in dementia. This knowledge may be useful for targeting and testing new AD treatments.
TITLE: Accumulation of Cerebrospinal Fluid Glycerophospholipids and Sphingolipids in Cognitively Healthy Participants With Alzheimer’s Biomarkers Precedes Lipolysis in the Dementia Stage
By: Frontiers in Neuroscience
Article type: Original Research
Authors: Alfred N Fonteh, Abby J Chiang, Xianghong Arakaki, Sarah Edminster, Michael G Harrington
Manuscript ID: 611393
Date: December 16, 2020