Abstract
INTRODUCTION
This study investigates primary lateral sclerosis (PLS) as a rare manifestation of the presenilin 1 (PSEN1) NM_000021 c.851C > T p.Pro284Leu variant in three siblings of a Colombian family, outlining its clinical and neuropathological features and their relationship to Alzheimer’s disease (AD).
METHODS
Data were gathered using clinical evaluations, next-generation genetic sequencing, magnetic resonance imaging, biomarker analysis, and neuropathological examination.
RESULTS
Carriers of the PSEN1 Pro284Leu variant exhibited classic PLS symptoms, including unilateral onset and bulbar syndromes, along with cognitive decline. Neuropathology showed corticospinal tract degeneration without amyloid beta deposition in spinal white matter.
DISCUSSION
Our findings suggest an overlap between PLS and AD pathology in PSEN1 variant carriers. Results support considering PLS when diagnosing AD-related motor syndromes and including PSEN1 evaluation when performing genetic testing for PLS. The study highlights the need for further research to clarify the PLS–AD relationship, informing future treatments and clinical trials.
Highlights
Pathogenic variants in presenilin 1 (PSEN1) can manifest as hereditary primary lateral sclerosis
PSEN1 Pro284Leu carriers present motor, cognitive, and behavioral alterations
Cases had corticospinal tract microgliosis and severe Aβ pathology in motor cortex
There was no evidence of amyloid deposition in the spinal cord white matter
All the neuropathology images are available for online visualization
Myelin pallor in the spinal cord is confined to the lateral corticospinal tracts
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This post is Copyright: Juliana Acosta‐Uribe,
Andrés Villegas‐Lanau,
Dionis Vallejo,
Laura Ramírez‐Aguilar,
Juan M. Solano,
Bárbara Mejía‐Cupajita,
David Aguillón,
Sonia Moreno,
Luis G. Méndez,
Ana Baena,
Lucía Madrigal,
Yamile Bocanegra,
Yakeel T. Quiroz,
Gloria P. García,
Daniel Vasquez,
Andrés Arbeláez,
Francisco Lopera,
Thomas G. Beach,
Kenneth S. Kosik,
Charles L. White III,
Margarita Giraldo‐Chica | July 28, 2024