Basal forebrain atrophy along the Alzheimer's disease continuum in adults with Down syndrome

Mateus Rozalem Aranha; Maria Florencia Iulita; Victor Montal; Jordi Pegueroles; Alexandre Bejanin; Lídia Vaqué-Alcázar; Michel J Grothe; Maria Carmona-Iragui; Laura Videla; Bessy Benejam; Javier Arranz; Concepción Padilla; Sílvia Valldeneu; Isabel Barroeta; Miren Altuna; Susana Fernández; Laia Ribas; Natalia Valle-Tamayo; Daniel Alcolea; Sofía González-Ortiz; Núria Bargalló; Henrik Zetterberg; Kaj Blennow; Rafael Blesa; Thomas Wisniewski; Jorge Busciglio; A Claudio Cuello; Alberto Lleó; Juan Fortea

doi:10.1002/alz.12999

Basal forebrain atrophy along the Alzheimer's disease continuum in adults with Down syndrome

Alzheimers Dement. 2023 Nov;19(11):4817-4827. doi: 10.1002/alz.12999. Epub 2023 Apr 6.

Authors

Mateus Rozalem Aranha^{1

2}, Maria Florencia Iulita^{1

2}, Victor Montal^{1

2}, Jordi Pegueroles^{1

2}, Alexandre Bejanin^{1

2}, Lídia Vaqué-Alcázar^{3

4

5}, Michel J Grothe^{2

6}, Maria Carmona-Iragui^{1

2

7}, Laura Videla^{1

2

7}, Bessy Benejam^{1

2

7}, Javier Arranz¹, Concepción Padilla^{1

2}, Sílvia Valldeneu^{1

2}, Isabel Barroeta^{1

2}, Miren Altuna^{1

2}, Susana Fernández⁷, Laia Ribas^{1

2}, Natalia Valle-Tamayo^{1

2}, Daniel Alcolea^{1

2}, Sofía González-Ortiz^{8

9}, Núria Bargalló^{9

10}, Henrik Zetterberg^{11

12

13

14

15}, Kaj Blennow^{12

14}, Rafael Blesa^{1

2}, Thomas Wisniewski¹⁶, Jorge Busciglio¹⁷, A Claudio Cuello^{18

19

20

21}, Alberto Lleó^{1

2}, Juan Fortea^{1

2

7}

Affiliations

¹ Sant Pau Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Institut d'Investigació Biomèdica Sant Pau (IIB SANT PAU), Facultad de Medicina - Universitat Autònoma de Barcelona, Barcelona, Spain.
² Center of Biomedical Investigation Network for Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
³ Institute of Neurosciences, Universitat de Barcelona, Barcelona, Spain.
⁴ Department of Medicine, Faculty of Medicine and Health Sciences, Universitat de Barcelona, Barcelona, Spain.
⁵ Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
⁶ Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
⁷ Barcelona Down Medical Center, Fundació Catalana de Síndrome de Down, Barcelona, Spain.
⁸ Hospital del Mar - Parc de Salut Mar, Barcelona, Spain.
⁹ Neuroradiology Section, Radiology Department, Diagnostic Image Center, Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona, Spain.
¹⁰ Magnetic Resonance Image Core Facility (IDIBAPS), Barcelona, Spain.
¹¹ Queen Square Institute of Neurology, University College London, London, UK.
¹² Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
¹³ UK Dementia Research Institute, University College London, London, UK.
¹⁴ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
¹⁵ Hong Kong Center for Neurodegenerative Diseases, China, Hong Kong.
¹⁶ Departments of Neurology, Pathology and Psychiatry and Center for Cognitive Neurology, New York University Grossman School of Medicine, New York, New York, USA.
¹⁷ Department of Neurobiology & Behavior, Institute for Memory Impairments and Neurological Disorders (iMIND), Center for the Neurobiology of Learning and Memory, University of California at Irvine, Irvine, California, USA.
¹⁸ Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
¹⁹ Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.
²⁰ Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada.
²¹ Department of Pharmacology, Oxford University, Oxford, UK.

PMID: 37021589
DOI: 10.1002/alz.12999

Abstract

Background: Basal forebrain (BF) degeneration occurs in Down syndrome (DS)-associated Alzheimer's disease (AD). However, the dynamics of BF atrophy with age and disease progression, its impact on cognition, and its relationship with AD biomarkers have not been studied in DS.

Methods: We included 234 adults with DS (150 asymptomatic, 38 prodromal AD, and 46 AD dementia) and 147 euploid controls. BF volumes were extracted from T-weighted magnetic resonance images using a stereotactic atlas in SPM12. We assessed BF volume changes with age and along the clinical AD continuum and their relationship to cognitive performance, cerebrospinal fluid (CSF) and plasma amyloid/tau/neurodegeneration biomarkers, and hippocampal volume.

Results: In DS, BF volumes decreased with age and along the clinical AD continuum and significantly correlated with amyloid, tau, and neurofilament light chain changes in CSF and plasma, hippocampal volume, and cognitive performance.

Discussion: BF atrophy is a potentially valuable neuroimaging biomarker of AD-related cholinergic neurodegeneration in DS.

Keywords: Alzheimer's disease; Down syndrome; basal forebrain; biomarkers; cholinergic; magnetic resonance imaging; neuroimaging; volumetry.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Adult
Alzheimer Disease* / pathology
Atrophy / pathology
Basal Forebrain*
Biomarkers / cerebrospinal fluid
Down Syndrome* / complications
Down Syndrome* / diagnostic imaging
Humans

Substances

Biomarkers

Abstract

Publication types

MeSH terms

Substances

Grants and funding