1. Elevated Norepinephrine Metabolism Gauges Alzheimer’s Disease-Related Pathology and Memory Decline
- Author
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Heidi I.L. Jacobs, Joost M. Riphagen, Maxime van Egroo, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, and Psychiatrie & Neuropsychologie
- Subjects
0301 basic medicine ,NATIONAL INSTITUTE ,Male ,Disease ,Neuropsychological Tests ,RECOMMENDATIONS ,Methoxyhydroxyphenylglycol ,memory ,Cohort Studies ,0302 clinical medicine ,Norepinephrine metabolism ,tau ,biology ,PLASMA ,General Neuroscience ,DEMENTIA ,General Medicine ,Middle Aged ,MHPG ,Pathophysiology ,Psychiatry and Mental health ,Clinical Psychology ,LOCUS-COERULEUS ,Disease Progression ,Female ,Amyloid-beta ,ASSOCIATION WORKGROUPS ,medicine.drug ,medicine.medical_specialty ,Amyloid beta ,Short Communication ,tau Proteins ,norepinephrine ,03 medical and health sciences ,Norepinephrine ,Alzheimer Disease ,Predictive Value of Tests ,Internal medicine ,medicine ,Humans ,Learning ,Amyloid-β ,Cognitive Dysfunction ,Aged ,Memory Disorders ,Amyloid beta-Peptides ,business.industry ,locus coeruleus ,Memory clinic ,Disease progression ,030104 developmental biology ,Endocrinology ,biology.protein ,Locus coeruleus ,DIAGNOSTIC GUIDELINES ,Geriatrics and Gerontology ,business ,030217 neurology & neurosurgery - 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.
- Published
- 2021