Locus coeruleus catecholamines link neuroticism and vulnerability to tau pathology in aging

Higher neuroticism is a risk factor for Alzheimer's disease (AD), and is implicated in disordered stress responses. The locus coeruleus (LC)-catecholamine system is activated during perceived threat and is a centerpiece of developing models of the pathophysiology of AD, as it is the first brain region to develop abnormal tau. We examined relationships among the "Big 5" personality traits, LC catecholamine synthesis capacity measured with [¹⁸F]Fluoro-m-tyrosine PET, and tau burden measured with [¹⁸F]Flortaucipir PET in cognitively normal older adults (n = 47). β-amyloid (Aβ) status was determined using [¹¹C]Pittsburgh compound B PET (n = 14 Aβ positive). Lower LC catecholamine synthesis capacity was associated with higher neuroticism, more depressive symptoms as measured by the Geriatric Depression Scale, and higher amygdala tau-PET binding. Exploratory analyses with other personality traits revealed that low trait conscientiousness was also related to both lower LC catecholamine synthesis capacity, and more depressive symptoms. A significant indirect path linked both high neuroticism and low conscientiousness to greater amygdala tau burden via their mutual association with low LC catecholamine synthesis capacity. Together, these findings reveal LC catecholamine synthesis capacity to be a promising marker of affective health and pathology burden in aging, and identifies candidate neurobiological mechanisms for the effect of personality on increased vulnerability to dementia.