TY  - JOUR
AU  - Fleck, Lara
AU  - Buss, Claudia
AU  - Bauer, Martin
AU  - Stein, Maike
AU  - Mekle, Ralf
AU  - Kock, Lena
AU  - Klawitter, Heiko
AU  - Godara, Malvika
AU  - Ramler, Judith
AU  - Entringer, Sonja
AU  - Endres, Matthias
AU  - Heim, Christine
TI  - Early-Life Adversity Predicts Markers of Aging-Related Neuroinflammation, Neurodegeneration, and Cognitive Impairment in Women.
JO  - Annals of neurology
VL  - 97
IS  - 4
SN  - 0364-5134
CY  - Hoboken, NJ
PB  - Wiley-Blackwell
M1  - DZNE-2025-00419
SP  - 642 - 656
PY  - 2025
AB  - Despite the overwhelming evidence for profound and longstanding effects of early-life stress (ELS) on inflammation, brain structure, and molecular aging, its impact on human brain aging and risk for neurodegenerative disease is poorly understood. We examined the impact of ELS severity in interaction with age on blood-based markers of neuroinflammation and neurodegeneration, brain volumes, and cognitive function in middle-aged women.We recruited 179 women (aged 30-60 years) with and without ELS exposure before the onset of puberty. Using Simoa technology, we assessed blood-based markers of neuroinflammation and neurodegeneration, including serum concentrations of glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL). We further obtained T1-weighted and T2-weighted magnetic resonance images to assess brain volumes and we assessed cognitive performance sensitive to early impairments associated with the development of dementia, using the Cambridge Neuropsychological Automated Test Battery. We used generalized additive models to examine nonlinear interaction effects of ELS severity and age on these outcomes.Analyses revealed significant nonlinear interaction effects of ELS severity and age on NfL and GFAP serum concentrations, total and subcortical gray matter volume loss, increased third ventricular volume, and cognitive impairment.These findings suggest that ELS profoundly exacerbates peripheral, neurostructural, and cognitive markers of brain aging. Our results are critical for the development of novel early prevention strategies that target the impact of developmental stress on the brain to mitigate aging-related neurological diseases. ANN NEUROL 2025;97:642-656.
KW  - Humans
KW  - Female
KW  - Middle Aged
KW  - Cognitive Dysfunction: blood
KW  - Cognitive Dysfunction: diagnostic imaging
KW  - Adult
KW  - Aging: pathology
KW  - Neurodegenerative Diseases: blood
KW  - Neurodegenerative Diseases: diagnostic imaging
KW  - Biomarkers: blood
KW  - Adverse Childhood Experiences
KW  - Neurofilament Proteins: blood
KW  - Neuroinflammatory Diseases: diagnostic imaging
KW  - Neuroinflammatory Diseases: blood
KW  - Neuroinflammatory Diseases: pathology
KW  - Glial Fibrillary Acidic Protein: blood
KW  - Magnetic Resonance Imaging
KW  - Brain: diagnostic imaging
KW  - Brain: pathology
KW  - Biomarkers (NLM Chemicals)
KW  - Neurofilament Proteins (NLM Chemicals)
KW  - Glial Fibrillary Acidic Protein (NLM Chemicals)
KW  - neurofilament protein L (NLM Chemicals)
KW  - GFAP protein, human (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:39786167
C2  - pmc:PMC11889533
DO  - DOI:10.1002/ana.27161
UR  - https://pub.dzne.de/record/277508
ER  -