HAI Book 2025 - Flipbook - Page 352
Koops, Elouise
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Lower LC-EC tract integrity is associated with entorhinal tau in
autosomal-dominant Alzheimer9s disease
Elouise Koops1, Averi Giudicessi2, Nikole Bonillas-Felix2, Randy Medrano2, Lusiana Martinez2,
Isabella Gonzalez2, Sergio Alvarez4, David Aguillon3, Yakeel T. Quiroz2,3,6, Heidi Jacobs1,5
1
Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard
Medical School, Boston, MA, US
2
Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, US
3
Neuroscience Group of Antioquia, Medicine School, University of Antioquia, Medellín, CO
4
Department of Radiology, Hospital Pablo Tobón Uribe, Medellín, CO
5
Faculty of Health, Medicine and Life Sciences, School for Mental Health and Neuroscience, Alzheimer Centre
Limburg, Maastricht University, Maastricht, NL
6
Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, US
Background: Autopsy studies indicate that the locus coeruleus (LC) is one of the first regions accumulating tau in
autosomal and sporadic AD before it becomes detectable in the entorhinal cortex (EC). As tau is assumed to
spread trans-axonally, it can be hypothesized that this process is associated with LC-EC tract degradation. While
LC-EC tract degradation has been reported in sporadic AD, it remains unknown whether LC-EC tract degradation
occurs in autosomal-dominant Alzheimer9s disease (ADAD) and is associated with entorhinal tau pathology.
Methods: We investigated the LC-EC white matter tract with diffusion-weighted imaging in the COLombiaBOSton cohort with PSEN1-E280A mutation (n=30) and healthy controls (n=33;Table 1) using fixel-based analyses
and tractography. Clinical status was defined with the Functional Assessment Staging Test (FAST). The MMSE and
the CERAD Word List were used to measure cognition. Multiple linear regressions related LC-EC tract
characteristics to age to disease onset, sex, PET-derived entorhinal tau burden, and cognition.
Results: Fiber-bundle cross-section (FC) of the LC-EC tract was lower for female than male participants
(p
