How Circulating Metabolites Can Predict Alzheimer's Pathogenesis
The investigators attempted to estimate the metabolic features of genetic liability to Alzheimer's disease (AD) at seven different stages across the life span, with the aim of identifying early features of AD pathogenesis that may be potential targets to prevent the clinical onset of AD. They designed a genetic instrument for AD liability and explored its association with circulating metabolites measured in two studies: the Avon Longitudinal Study of Parents and Children (ALSPAC) and the UK Biobank. The results bolster a deep-seated influence of the APOE4 isoform on circulating lipids and fatty acids from early life to later adulthood. These lipid and fatty acid traits may be involved in early AD pathogenesis. AD-associated metabolic disorders take root in childhood, multiple decades before the development of disease, and carry over into later adulthood when the diagnosis of AD more commonly occurs.
@lipi Amid our aging population, the number of patients with AD — the most common form of dementia — continues to increase. Neuropathological hallmarks of AD arise decades earlier than the onset of clinical symptoms, yet patients are often diagnosed late in the disease trajectory. Although brain and cerebrospinal fluid (CSF) metabolites differentiate AD cases from controls with a high level of accuracy, they require invasive methods, such as lumbar puncture, to collect samples. As a result, significant motivation remains for more easily identifying measured plasma AD biomarkers, as is starting to be shown for plasma amyloid-beta, which could enhance our understanding of early disease etiology.