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

Affiliations

¹ Department of Psychology, Brandeis University, Waltham, MA, 02453, USA. Electronic address: jourdanparent@brandeis.edu.
² Department of Psychology, Brandeis University, Waltham, MA, 02453, USA.
³ Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA, 94720, USA.
⁴ Institute of Cognitive Neurology and Dementia Research, Otto von Guericke University, Magdeburg, 39106, Germany; Deutsches Zentrum für Neurodegenerative Erkrankungen, Magdeburg, 39120, Germany; Center for Behavioral Brain Sciences, University of Magdeburg, Magdeburg, Germany.
⁵ Deutsches Zentrum für Neurodegenerative Erkrankungen, Magdeburg, 39120, Germany.
⁶ Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA, 94720, USA; Lawrence Berkeley National Laboratory, Berkeley, CA, 94720, USA.
⁷ Department of Psychology, Brandeis University, Waltham, MA, 02453, USA; Lawrence Berkeley National Laboratory, Berkeley, CA, 94720, USA.

PMID: 36191755
PMCID: PMC10060440
DOI: 10.1016/j.neuroimage.2022.119658

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

Jourdan H Parent et al. Neuroimage. 2022 Nov.

. 2022 Nov:263:119658.

doi: 10.1016/j.neuroimage.2022.119658. Epub 2022 Sep 30.

Authors

Affiliations

¹ Department of Psychology, Brandeis University, Waltham, MA, 02453, USA. Electronic address: jourdanparent@brandeis.edu.
² Department of Psychology, Brandeis University, Waltham, MA, 02453, USA.
³ Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA, 94720, USA.
⁴ Institute of Cognitive Neurology and Dementia Research, Otto von Guericke University, Magdeburg, 39106, Germany; Deutsches Zentrum für Neurodegenerative Erkrankungen, Magdeburg, 39120, Germany; Center for Behavioral Brain Sciences, University of Magdeburg, Magdeburg, Germany.
⁵ Deutsches Zentrum für Neurodegenerative Erkrankungen, Magdeburg, 39120, Germany.
⁶ Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA, 94720, USA; Lawrence Berkeley National Laboratory, Berkeley, CA, 94720, USA.
⁷ Department of Psychology, Brandeis University, Waltham, MA, 02453, USA; Lawrence Berkeley National Laboratory, Berkeley, CA, 94720, USA.

PMID: 36191755
PMCID: PMC10060440
DOI: 10.1016/j.neuroimage.2022.119658

Abstract

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.

Keywords: Aging; Conscientiousness; Locus coeruleus; Neuroticism; Tau.

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Conflict of interest statement

Declaration of Competing Interest Dr. Jagust has served as a consultant to Biogen and Bioclinica, and holds an equity interest in Optoceutics. All other authors have no financial disclosures.

Figures

**Fig. 1.. Plot of the time from FMT scan.**
Individual subject data are plotted to display the temporal relationship of FTP PET (blue), PiB negative PET (green), and PiB positive PET (red) relative to FMT PET (pink). Subjects are ranked by LC FMT value for (1 = lowest, 47 = highest). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

**Fig. 2.. Relationships among neuroticism, FMT, and Geriatric Depression Risk.**
(A) Scatterplot of correlation between neuroticism and GDS scores. (B) dorsal raphe (blue) and locus coeruleus (LC) (green) regions-of-interest overlayed on sample-specific older adult template brain. (C-D) Scatterplots show LC FMT relationship with neuroticism (C) and GDS (D). (E-F) Scatterplots show dorsal raphe FMT relationship with neuroticism (E) and GDS (F). 90% confidence intervals are depicted. Circles indicate PiB negative individuals, triangles indicate PiB positive individuals. *p < .05, **p < .01, ***p < .001. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

**Fig. 3.. Relationships among neuroticism, FMT and amygdala FTP.**
(A) Scatterplot of correlation between neuroticism and amygdala FTP. (B) Scatterplot of correlation between GDS and amygdala FTP. (C) Scatterplots show LC FMT relationship with amygdala FTP. (D) Scatterplots show raphe FMT relationship with amygdala FTP. 90% confidence intervals are depicted. Circles indicate PiB negative individuals, triangles indicate PiB positive individuals. *p < .05.

**Fig. 4.. Relationships among conscientiousness, LC FMT, and amygdala FTP.**
(A) Scatterplot of correlation between conscientiousness and GDS. (B) Scatterplot of correlation between conscientiousness and LC FMT. (C) Scatterplot of the relationship between conscientiousness and amygdala FTP. 90% confidence intervals are depicted. Circles indicate PiB negative individuals, triangles indicate PiB positive individuals. *p < .05, **p < .01.

**Fig. 5.. Bidirectional model of locus coeruleus catecholamine synthesis and personality traits.**
We propose that relations between personality traits and catecholamine synthesis in the locus coeruleus (LC) has several implications in aging. Personality traits that affect an individual’s sensitivity or exposure to stress may contribute to reductions in LC catecholamine synthesis. Altered LC catecholamine function and engagement of LC-amygdala pathways may then result in increased tau accumulation in the amygdala. Additionally, amygdala tau accumulation may cause decreases in LC catecholamine synthesis, which, in turn, may alter cognitive and affective function. NE = norepinephrine.

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References

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

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

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Conflict of interest statement

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