Hayley R. Shanks, Canada
University of Western Ontario Schulich Medicine and DentistryPresenter of 2 Presentations
LIVE DISCUSSION
SERUM PHOSPHATIDYLCHOLINE SELECTIVELY PREDICTS LONGITUDINAL BASAL FOREBRAIN DEGENERATION IN ALZHEIMER’S DISEASE
Abstract
Aims
Reduced cholinergic neurotransmission resulting from basal forebrain degeneration causes cognitive impairment in Alzheimer’s disease (AD). The underlying causes of cholinergic degeneration are poorly understood. We assessed whether AD-related reductions in the bioavailability of the lipid phosphatidylcholine potentiates vulnerability of cholinergic basal forebrain neurons. Cholinergic neurons may place high demand on phosphatidylcholine lipid pathways because they are large, highly plastic, and use phosphatidylcholine to synthesize acetylcholine. An AD-related bottleneck on phosphatidylcholine may therefore impact cholinergic neuronal functions earlier and more severely than other cell types.
Methods
We leveraged data from the Alzheimer’s Disease Neuroimaging Initiative. Participants were stratified according to cerebrospinal fluid (CSF) ratios of amyloid and tau into age-matched normal (n = 62) and abnormal (n = 161) CSF groups. Longitudinal structural magnetic resonance imaging data were used to quantify grey matter degeneration for each participant. Partial least squares analyses assessed the multivariate relationship between serum lipids, including phosphatidylcholine, and neuroimaging data.
Results
Of all serum lipids, phosphatidylcholine (p = 0.002 on 5000 permutations) and acylcarnitine (p = 0.003 on 5000 permutations) were the only lipid types to exhibit a relationship with grey matter degeneration which was modified by CSF-confirmed AD pathology. The relationship between phosphatidylcholine and longitudinal grey matter degeneration revealed a spatial pattern (Figure, blue) with high anatomical specificity to brain regions known to be cholinergic, such as the basal forebrain and striatum.
Conclusions
We provide in vivo evidence for a selective relationship between phosphatidylcholine and basal forebrain degeneration, suggesting that phosphatidylcholine levels may be a risk factor for preclinical AD.