Linking higher amyloid beta 1‐38 (Aβ(1‐38)) levels to reduced Alzheimer's disease progression risk

Schneider, Luisa Sophie ; Freiesleben, Silka Dawn; Breukelen, Gerard van; Wang, Xiao; Brosseron, Frederic; Heneka, Michael T.; Teipel, Stefan; Kleineidam, Luca; Stark, Melina; Roy‐Kluth, Nina; Wagner, Michael; Spottke, Annika; Schmid, Matthias; Roeske, Sandra; Laske, Christoph; Munk, Matthias H.; Perneczky, Robert ; Rauchmann, Boris‐Stephan; Buerger, Katharina ; Janowitz, Daniel ; Düzel, Emrah; Glanz, Wenzel; Jessen, Frank; Rostamzadeh, Ayda; Wiltfang, Jens; Bartels, Claudia; Kilimann, Ingo; Schneider, Anja; Fliessbach, Klaus; Priller, Josef ; Spruth, Eike Jakob; Hellmann‐Regen, Julian und Peters, Oliver (2025): Linking higher amyloid beta 1‐38 (Aβ(1‐38)) levels to reduced Alzheimer's disease progression risk. In: Alzheimer's & Dementia, Bd. 21, Nr. 2, e14545

Abstract

Introduction: The beneficial effects of amyloid beta 1-38, or Aβ(1-38), onAlzheimer’s disease (AD) progression in humans in vivo remain controversial. Weinvestigated AD patients’ cerebrospinal fluid (CSF) Aβ(1-38) and AD progression.

Methods: Cognitive function and diagnostic change were assessed annually for3 years in 177 Aβ-positive participants with subjective cognitive decline (SCD),mild cognitive impairment (MCI), and dementia from the German Center for Neu-rodegenerative Diseases (DZNE) longitudinal cognitive impairment and dementiastudy (DELCODE) cohort using the Mini-Mental State Examination (MMSE), Pre-clinical Alzheimer’s Cognitive Composite (PACC), Clinical Dementia Rating (CDR),and National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer’s Disease and Related Disorders Association (NINCDS-ADRDA) criteria.Mixed linear and Cox regression analyses were conducted. CSF was collected atbaseline.

Results: Higher Aβ(1-38) levels were associated with slower PACC (p = 0.001) andslower CDR Sum of Boxes (CDR-SB) (p = 0.002) but not MMSE decline. Including Aβ(1-40) beyond Aβ(1-38) in the model confirmed an association of Aβ(1-38) with slowerPACC decline (p = 0.005), but not with CDR-SB or MMSE decline. In addition, higherAβ(1-38) baseline levels were associated with a reduced dementia conversion risk.

Discussion: Further research is needed to understand the role of Aβ(1-38) in AD andits potential for future therapeutic strategies.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin > Munich Cluster for Systems Neurology (SyNergy) ; Medizin > Institut für Schlaganfall- und Demenzforschung (ISD) ; Medizin > Klinikum der LMU München > Klinik und Poliklink für Psychiatrie und Psychotherapie ; Medizin > Klinikum der LMU München > Klinik und Poliklinik für Radiologie
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1552-5260
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198