Title | Elevated Norepinephrine Metabolism Gauges Alzheimer's Disease-Related Pathology and Memory Decline. |
Publication Type | Journal Article |
Year of Publication | 2021 |
Authors | Riphagen, JM, van Egroo, M, Jacobs, HIL |
Journal | J Alzheimers Dis |
Volume | 80 |
Issue | 2 |
Pagination | 521-526 |
Date Published | 2021 |
ISSN | 1875-8908 |
Keywords | Aged, Alzheimer Disease, Amyloid beta-Peptides, Cognitive Dysfunction, Cohort Studies, Disease Progression, Female, Humans, Learning, Locus Coeruleus, Male, Memory Disorders, Methoxyhydroxyphenylglycol, Middle Aged, Neuropsychological Tests, Norepinephrine, Predictive Value of Tests, tau Proteins |
Abstract | The noradrenergic (NE) locus coeruleus (LC) is vulnerable to hyperphosphorylated tau, and dysregulated NE-metabolism is linked to greater tau and disease progression. We investigated whether elevated NE-metabolism alone predicts memory decline or whether concomitant presence of tau and amyloid-β is required. Among 114 memory clinic participants, time trends (max. six years) showed dose-response declines in learning across groups with elevated NE-metabolite 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) with no, one, or two Alzheimer's disease biomarkers; and no decline in the low MHPG group. Elevated MHPG is required and sufficient to detect learning declines, supporting a pathophysiologic model including the LC-NE system contributing to initial Alzheimer's disease-related processes. |
DOI | 10.3233/JAD-201411 |
Alternate Journal | J Alzheimers Dis |
PubMed ID | 33554915 |
PubMed Central ID | PMC8075385 |
Grant List | R01 AG062559 / AG / NIA NIH HHS / United States |