The purpose of this study is to test the safety, tolerability, and effects of choline in people with increased risk of Alzheimer's Disease (AD), also known as pre-symptomatic AD. Choline is a dietary supplement, but is being investigated to see if it has any effects on the progression to AD.
The purpose of this study is to determine the safety and tolerability, as well as the biochemical effects of choline bitartrate over a 6-month treatment period in a moderately sized population harboring at least one copy of the APOE4 gene. APOE is a protein involved in lipid transport. Studies show that the APOE4 variant is strongly associated with an increased risk of Alzheimer's Disease. It is unclear how APOE4 results in an increased risk for AD, but a recent study identified a novel molecular pathway, which showed that APOE4-induced dysfunction of lipid metabolism in neurons by cellular accumulation of unsaturated lipids. The investigators hypothesize that choline supplementation normalizes the APOE4-mediated dysregulation by normalizing the Kennedy pathway in neuronal cells, thus stabilizing the lipid metabolism and concomitantly restoring normal cell function by increasing phosphatidylcholine activity via the Kennedy pathway. To evaluate this, the investigators will test if choline supplementation will decrease the ratio of unsaturated lipids to saturated lipids (the fatty acid desaturation index) in cerebrospinal fluid by 15% and increase phosphatidylcholine by 100%.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
15
Eight 275mg capsules taken orally twice daily (4 capsules with breakfast \& 4 capsules with dinner) x 180 days
The University of Texas Health Science Center at Houston (UTHealth)
Houston, Texas, United States
Changes in the fatty acid desaturation index (FADI) in the CSF following choline supplementation
FADI will be utilized to determine whether unsaturated to saturated lipids decreases by 15%
Time frame: baseline, 6 months
Changes in phosphatidylcholine (PC) in the CSF following choline supplementation
FADI ( fatty acid desaturation index) will be utilized to determine whether saturated PC increases by 100%
Time frame: baseline, 6 months
Number of participants with treatment-related adverse events
Safety endpoints will be monitored throughout the study and number of incidents reported at end of study. Aggregate values and percentages will be reported
Time frame: 9 months
Changes in phospholipids in CSF following choline supplementation
Will compare scaled intensity between baseline and 6 months.
Time frame: Baseline and 6 months
Changes in phosphatidylcholine in blood following choline supplementation
Aggregate values and percentages will be reported.
Time frame: Baseline and 6 months
Changes in choline in blood following choline supplementation
Aggregate values and percentages will be reported
Time frame: Baseline and 6 months
Changes in proinflammatory cytokines in blood plasma following choline supplementation
Proinflammatory cytokine panel in plasma will be measured using commercially available immunosorbent assays to determine potential treatment effects. Aggregate values and percentages will be reported. Each sample will be tested in triplicate.
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Time frame: Baseline and 6 months
Changes in neurofilament light chain (Nf-L) in CSF following choline supplementation
Levels of NfL in CSF will be measured using commercially available immunosorbent assays to determine potential treatment effects. Aggregate values and percentages will be reported. Each sample will be tested in triplicate.
Time frame: Baseline and 6 months
Changes in amyloid-β 42/40 ratio CSF following choline supplementation
Levels of amyloid-β 42/40 ratio in CSF will be measured by LC/MS/MS assays. Aggregate values and percentages will be reported.
Time frame: Baseline and 6 months
Changes in p-Tau/Total Tau ratio in CSF following choline supplementation
Levels of p-Tau/Total Tau will be measured by LC/MS/MS assays. Aggregate values and percentages will be reported.
Time frame: Baseline and 6 months