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APOE ϵ4 genotype-dependent cerebrospinal fluid proteomic signatures in Alzheimer's disease
- Source :
- Konijnenberg, E, Tijms, B M, Gobom, J, Dobricic, V, Bos, I, Vos, S, Tsolaki, M, Verhey, F, Popp, J, Martinez-Lage, P, Vandenberghe, R, Lleó, A, Frölich, L, Lovestone, S, Streffer, J, Bertram, L, Blennow, K, Teunissen, C E, Veerhuis, R, Smit, A B, Scheltens, P, Zetterberg, H & Visser, P J 2020, ' APOE ϵ4 genotype-dependent cerebrospinal fluid proteomic signatures in Alzheimer's disease ', Alzheimer's Research and Therapy, vol. 12, 65, pp. 1-11 . https://doi.org/10.1186/s13195-020-00628-z, Alzheimer's Research and Therapy, 12:65, 1-11. BioMed Central, Alzheimers Research & Therapy, r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau, instname, Alzheimer's research & therapy, vol. 12, no. 1, pp. 65, Alzheimer's Research and Therapy, 12(1):65. BioMed Central, Alzheimer’s Research & Therapy, Vol 12, Iss 1, Pp 1-11 (2020), Konijnenberg, E, Tijms, B M, Gobom, J, Dobricic, V, Bos, I, Vos, S, Tsolaki, M, Verhey, F, Popp, J, Martinez-Lage, P, Vandenberghe, R, Lleó, A, Frölich, L, Lovestone, S, Streffer, J, Bertram, L, Blennow, K, Teunissen, C E, Veerhuis, R, Smit, A B, Scheltens, P, Zetterberg, H & Visser, P J 2020, ' APOE ϵ4 genotype-dependent cerebrospinal fluid proteomic signatures in Alzheimer's disease ', Alzheimer's Research and Therapy, vol. 12, no. 1, 65 . https://doi.org/10.1186/s13195-020-00628-z, Alzheimer's Research & Therapy, 12(1):65. BioMed Central Ltd, Alzheimer's Research & Therapy
- Publication Year :
- 2020
-
Abstract
- Background Aggregation of amyloid β into plaques in the brain is one of the earliest pathological events in Alzheimer’s disease (AD). The exact pathophysiology leading to dementia is still uncertain, but the apolipoprotein E (APOE) ε4 genotype plays a major role. We aimed to identify the molecular pathways associated with amyloid β aggregation using cerebrospinal fluid (CSF) proteomics and to study the potential modifying effects of APOE ε4 genotype. Methods We tested 243 proteins and protein fragments in CSF comparing 193 subjects with AD across the cognitive spectrum (65% APOE ε4 carriers, average age 75 ± 7 years) against 60 controls with normal CSF amyloid β, normal cognition, and no APOE ε4 allele (average age 75 ± 6 years). Results One hundred twenty-nine proteins (53%) were associated with aggregated amyloid β. APOE ε4 carriers with AD showed altered concentrations of proteins involved in the complement pathway and glycolysis when cognition was normal and lower concentrations of proteins involved in synapse structure and function when cognitive impairment was moderately severe. APOE ε4 non-carriers with AD showed lower expression of proteins involved in synapse structure and function when cognition was normal and lower concentrations of proteins that were associated with complement and other inflammatory processes when cognitive impairment was mild. Repeating analyses for 114 proteins that were available in an independent EMIF-AD MBD dataset (n = 275) showed that 80% of the proteins showed group differences in a similar direction, but overall, 28% effects reached statistical significance (ranging between 6 and 87% depending on the disease stage and genotype), suggesting variable reproducibility. Conclusions These results imply that AD pathophysiology depends on APOE genotype and that treatment for AD may need to be tailored according to APOE genotype and severity of the cognitive impairment.
- Subjects :
- Proteomics
0301 basic medicine
Apolipoprotein E
APOE genotype
lcsh:RC346-429
COMPLEMENT
0302 clinical medicine
Cerebrospinal fluid
Genotype
Amyloid aggregation
Aged, 80 and over
DEMENTIA
ASSOCIATION
Pathophysiology
PREVALENCE
ALLELE
Neurology
medicine.symptom
Life Sciences & Biomedicine
medicine.medical_specialty
Amyloid
Cognitive Neuroscience
BIOMARKERS
Clinical Neurology
tau Proteins
Inflammation
APOLIPOPROTEIN E4
CSF proteomics
lcsh:RC321-571
MICROGLIA
03 medical and health sciences
INFLAMMATION
Alzheimer Disease
Internal medicine
medicine
Humans
Dementia
lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry
lcsh:Neurology. Diseases of the nervous system
Aged
Amyloid beta-Peptides
Science & Technology
business.industry
Research
Neurosciences
Reproducibility of Results
medicine.disease
Complement system
POSTERIOR CINGULATE
030104 developmental biology
Endocrinology
Neurology (clinical)
Neurosciences & Neurology
business
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 17589193
- Database :
- OpenAIRE
- Journal :
- Konijnenberg, E, Tijms, B M, Gobom, J, Dobricic, V, Bos, I, Vos, S, Tsolaki, M, Verhey, F, Popp, J, Martinez-Lage, P, Vandenberghe, R, Lleó, A, Frölich, L, Lovestone, S, Streffer, J, Bertram, L, Blennow, K, Teunissen, C E, Veerhuis, R, Smit, A B, Scheltens, P, Zetterberg, H & Visser, P J 2020, ' APOE ϵ4 genotype-dependent cerebrospinal fluid proteomic signatures in Alzheimer's disease ', Alzheimer's Research and Therapy, vol. 12, 65, pp. 1-11 . https://doi.org/10.1186/s13195-020-00628-z, Alzheimer's Research and Therapy, 12:65, 1-11. BioMed Central, Alzheimers Research & Therapy, r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau, instname, Alzheimer's research & therapy, vol. 12, no. 1, pp. 65, Alzheimer's Research and Therapy, 12(1):65. BioMed Central, Alzheimer’s Research & Therapy, Vol 12, Iss 1, Pp 1-11 (2020), Konijnenberg, E, Tijms, B M, Gobom, J, Dobricic, V, Bos, I, Vos, S, Tsolaki, M, Verhey, F, Popp, J, Martinez-Lage, P, Vandenberghe, R, Lleó, A, Frölich, L, Lovestone, S, Streffer, J, Bertram, L, Blennow, K, Teunissen, C E, Veerhuis, R, Smit, A B, Scheltens, P, Zetterberg, H & Visser, P J 2020, ' APOE ϵ4 genotype-dependent cerebrospinal fluid proteomic signatures in Alzheimer's disease ', Alzheimer's Research and Therapy, vol. 12, no. 1, 65 . https://doi.org/10.1186/s13195-020-00628-z, Alzheimer's Research & Therapy, 12(1):65. BioMed Central Ltd, Alzheimer's Research & Therapy
- Accession number :
- edsair.doi.dedup.....1735b4dda9330a7d660bcf93e1af7672