Journal
NEURON
Volume 110, Issue 6, Pages 1009-+Publisher
CELL PRESS
DOI: 10.1016/j.neuron.2021.12.016
Keywords
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Categories
Funding
- German Center for Neurodegenerative Diseases (DZNE e.V.) within the Helmholtz Association
- PREADAPT project within the EU Joint Programs for Neurodegenerative Diseases Research (JPND) PERSOMED [01ED2007B]
- PREADAPT project within the JPND PERSOMED (German Federal Ministry of Education and Research [BMBF] grant [01ED1619A]
- Medical Research Council within the JPND PERSOMED (PREADAPT project) [MR/T046171/1]
- Instituto de Salud Carlos III (ISCIII) [FI20/00215]
- Grifols SA
- Fundacion bancaria La Caixa
- Fundacia ACE
- CIBERNED
- European Union/EFPIA Innovative Medicines Initiative joint undertaking ADAPTED project [115975]
- European Union/EFPIA Innovative Medicines Initiative joint undertaking MOPEAD project [115985]
- ISCIII-Subdireccion General de Evaluacion
- Fondo Europeo de Desarrollo Regional (FEDER-`Una manera de hacer Europa')
- JPco-fuND2 Multinational research projects on Personalised Medicine for Neurodegenerative Diseases''
- PREADAPT project (ISCIII grant) [AC19/00097]
- EURONANOMED III Joint Transnational call [AC17/00100]
- JPND grant GENFI-prox'' (by DLR/BMBF)
- European Union
- State of Saxony-Anhalt (Research Alliance Autonomy in Old Age'')
- [PI13/02434]
- [PI16/01861]
- [PI17/01474]
- [PI19/01240]
- [PI19/01301]
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Understanding neuroinflammation in Alzheimer's disease is crucial, as evident from the analysis of inflammatory biomarkers in pre-dementia individuals showing close interactions between inflammation and accumulating neurodegeneration. Additionally, higher levels of specific biomarkers are associated with larger brain structure and stable cognitive outcomes at follow-up.
There is an urgent need to improve the understanding of neuroinflammation in Alzheimer's disease (AD). We analyzed cerebrospinal fluid inflammatory biomarker correlations to brain structural volume and longitudinal cognitive outcomes in the DELCODE study and in a validation cohort of the F.ACE Alzheimer Center Barcelona. We investigated whether respective biomarker changes are evident before onset of cognitive impairment. YKL-40; sTREM2; sAXL; sTyro3; MIF; complement factors C1q, C4, and H; ferritin; and ApoE protein were elevated in pre-dementia subjects with pathological levels of tau or other neurodegeneration markers, demonstrating tight interactions between inflammation and accumulating neurodegeneration even before onset of symptoms. Intriguingly, higher levels of ApoE and soluble TAM receptors sAXL and sTyro3 were related to larger brain structure and stable cognitive outcome at follow-up. Our findings indicate a protective mechanism relevant for intervention strategies aiming to regulate neuroinflammation in subjects with no or subjective symptoms but underlying AD pathology profile.
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