Journal of Aging Science

Abstract

Elevated Cerebrospinal Fluid Norepinephrine in the Elderly can Link Depression and a Reduced Glymphatic System as Risk Factors for Alzheimer’s Disease

Patricia Szot

Aging (>65 years) is clearly the greatest risk factor for developing late-onset Alzheimer’s disease (AD), although the age of onset for an individual is unknown. Accumulation of plaques (Aβ) and tangles (phosphorylated tau) are believed to be the cause of AD and are considered the two major neuropathological markers of AD, and occurs well before the appearance of cognitive impairment. Reducing the incidence of AD by reducing the accumulation of plaques or tangles could have a profound effect on the predicted costs of caring for these individuals. To reduce the incidence or delay the onset of AD in the elderly population, risk factors or biomarkers need to be identified very early in the progression of the disorder to indicate when interventions should be initiated to prevent or slow the progression of AD. This review hypothesizes that depression in the elderly is a marker of depression because it suggests the noradrenergic nervous system in the locus coeruleus (LC) is malfunctioning. The noradrenergic neurons in the LC are malfunctioning because there is a loss of noradrenergic neurons due to early stage AD pathology. The minimal loss of LC neurons increases synaptic brain norepinephrine (NE) levels which precipitates depression and a reduction in the glymphatic system. The reduction in the glymphatic system would reduce the clearance of Aβ and tau from the brain, thereby enhancing the deposition of plaques and tangles in the brain and the development of AD.