TY  - JOUR
AU  - Schneider, Luisa Sophie
AU  - Freiesleben, Silka Dawn
AU  - van Breukelen, Gerard
AU  - Wang, Xiao
AU  - Brosseron, Frederic
AU  - Heneka, Michael T
AU  - Teipel, Stefan
AU  - Kleineidam, Luca
AU  - Stark, Melina
AU  - Roy-Kluth, Nina
AU  - Wagner, Michael
AU  - Spottke, Annika
AU  - Schmid, Matthias
AU  - Roeske, Sandra
AU  - Laske, Christoph
AU  - Munk, Matthias H
AU  - Perneczky, Robert
AU  - Rauchmann, Boris Stephan
AU  - Buerger, Katharina
AU  - Janowitz, Daniel
AU  - Düzel, Emrah
AU  - Glanz, Wenzel
AU  - Jessen, Frank
AU  - Rostamzadeh, Ayda
AU  - Wiltfang, Jens
AU  - Bartels, Claudia
AU  - Kilimann, Ingo
AU  - Schneider, Anja
AU  - Fliessbach, Klaus
AU  - Priller, Josef
AU  - Spruth, Eike Jakob
AU  - Hellmann-Regen, Julian
AU  - Peters, Oliver
TI  - Linking higher amyloid beta 1-38 (Aβ(1-38)) levels to reduced Alzheimer's disease progression risk.
JO  - Alzheimer's and dementia
VL  - 21
IS  - 2
SN  - 1552-5260
CY  - Hoboken, NJ
PB  - Wiley
M1  - DZNE-2025-00385
SP  - e14545
PY  - 2025
AB  - The beneficial effects of amyloid beta 1-38, or Aβ(1-38), on Alzheimer's disease (AD) progression in humans in vivo remain controversial. We investigated AD patients' cerebrospinal fluid (CSF) Aβ(1-38) and AD progression.Cognitive function and diagnostic change were assessed annually for 3 years in 177 Aβ-positive participants with subjective cognitive decline (SCD), mild cognitive impairment (MCI), and dementia from the German Center for Neurodegenerative Diseases (DZNE) longitudinal cognitive impairment and dementia study (DELCODE) cohort using the Mini-Mental State Examination (MMSE), Preclinical 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 at baseline.Higher Aβ(1-38) levels were associated with slower PACC (p = 0.001) and slower 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 slower PACC decline (p = 0.005), but not with CDR-SB or MMSE decline. In addition, higher Aβ(1-38) baseline levels were associated with a reduced dementia conversion risk.Further research is needed to understand the role of Aβ(1-38) in AD and its potential for future therapeutic strategies.This study not only replicates but also extends the existing findings on the role of Aβ(1-38) (amyloid beta 1-38) in Alzheimer's disease (AD) in humans in vivo. Higher baseline Aβ(1-38) levels were associated with a decreased risk of conversion to AD dementia in subjective cognitive decline (SCD) and mild cognitive impairment (MCI). Different linear-mixed regression models suggest an association between higher Aβ(1-38) baseline levels and slower Preclinical Alzheimer's Cognitive Composite (PACC) and Clinical Dementia Rating Sum of Boxes (CDR-SB) decline. Including Aβ(1-40) beyond Aβ(1-38) in the model confirmed a link between Aβ(1-38) and PACC decline, but showed no association of Aβ(1-38) on CDR-SB and Mini-Mental State Examination (MMSE) decline. The impact of short Aβ isoforms in AD progression might have been under-investigated These findings underscore the urgent need for additional research on the role of these shorter Aβ peptides in AD, as they may hold key insights for future therapeutic strategies.
KW  - Humans
KW  - Amyloid beta-Peptides: cerebrospinal fluid
KW  - Alzheimer Disease: cerebrospinal fluid
KW  - Disease Progression
KW  - Male
KW  - Female
KW  - Peptide Fragments: cerebrospinal fluid
KW  - Aged
KW  - Cognitive Dysfunction: cerebrospinal fluid
KW  - Longitudinal Studies
KW  - Mental Status and Dementia Tests
KW  - Biomarkers: cerebrospinal fluid
KW  - Middle Aged
KW  - Aged, 80 and over
KW  - Neuropsychological Tests: statistics & numerical data
KW  - AD conversion risk (Other)
KW  - Alzheimer's disease (Other)
KW  - Aβ(1‐38) (Other)
KW  - cerebrospinal fluid (Other)
KW  - cognitive decline (Other)
KW  - neurotoxicity (Other)
KW  - protective factor (Other)
KW  - shorter Aβ peptides (Other)
KW  - Amyloid beta-Peptides (NLM Chemicals)
KW  - Peptide Fragments (NLM Chemicals)
KW  - amyloid beta-protein (1-38) (NLM Chemicals)
KW  - Biomarkers (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:39868793
C2  - pmc:PMC11863357
DO  - DOI:10.1002/alz.14545
UR  - https://pub.dzne.de/record/277323
ER  -